TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Đuriš, Jelena
AU  - Cvijić, Sandra
AU  - Crevar, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović-Stanojević, Nevena
AU  - Karanović, Danijela
AU  - Ivanov, Milan
AU  - Jovović, Đurđica
AU  - Vajić, Una-Jovana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4932
AB  - In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.
PB  - Elsevier
T2  - Journal of Drug Delivery Science and Technology
T1  - Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films
VL  - 86
DO  - 10.1016/j.jddst.2023.104715
ER  - 

@article{
author = "Kurćubić, Ivana and Đuriš, Jelena and Cvijić, Sandra and Crevar, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović-Stanojević, Nevena and Karanović, Danijela and Ivanov, Milan and Jovović, Đurđica and Vajić, Una-Jovana",
year = "2023",
abstract = "In order to exploit the advantage of drug delivery through the buccal mucosa, mucoadhesive buccal films with propranolol hydrochloride based on polyethylene oxide, hydroxypropyl methylcellulose, and polyvinyl alcohol have been developed. The aim of this study was the development, pharmaceutical-technological (uniformity of mass and drug content, film thickness, potential interactions between polymers and propranolol hydrochloride, in vitro drug permeation and drug release, mechanical and mucoadhesive properties), and biopharmaceutical characterization of prepared mucoadhesive buccal films through conducting in vivo study in spontaneously hypertensive rats and in silico modeling of intraoral and gastrointestinal drug absorption. For in vivo study formulation F2 (hydroxypropylmethyl cellulose 0.5%, polyethylene oxide 3.5%, polyvinyl alcohol 1.5%, propylene glycol 3%, and propranolol hydrochloride 2%) was selected, which showed the highest values of tensile strength and percentage of elongation, as well as the highest value of the force of adhesion. Results of pharmacokinetic in rats and in silico modeling confirmed the superiority of the mucoadhesive buccal films over immediate-release tablets (in rats: AUC0→24h 66.13 ± 18.03 vs. 24.61 ± 5.52 μg⋅h/mL, AUC0→∞ 111.82 ± 39.04 vs. 47.85 ± 11.67 μg⋅h/mL; in silico: AUC0→24h 200.17 vs.74.58 ng⋅h/mL, AUC0→∞ 204.04 vs. 75.64 ng⋅h/mL). Hemodynamic measurements have shown that mucoadhesive buccal films, compared to immediate-release tablets, provide a more pronounced decrease primarily in heart rate (28-51%), but also in diastolic pressure (up to 33%), as well as a longer heart rate reduction that was maintained for up to 12th h. Therefore, mucoadhesive buccal films increased the degree of absorbed drug and thus contributed to better therapeutic outcomes compared to immediate-release tablets for peroral administration.",
publisher = "Elsevier",
journal = "Journal of Drug Delivery Science and Technology",
title = "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films",
volume = "86",
doi = "10.1016/j.jddst.2023.104715"
}

Kurćubić, I., Đuriš, J., Cvijić, S., Crevar, M., Ibrić, S., Miloradović, Z., Mihailović-Stanojević, N., Karanović, D., Ivanov, M., Jovović, Đ.,& Vajić, U.. (2023). Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology
Elsevier., 86.
https://doi.org/10.1016/j.jddst.2023.104715

Kurćubić I, Đuriš J, Cvijić S, Crevar M, Ibrić S, Miloradović Z, Mihailović-Stanojević N, Karanović D, Ivanov M, Jovović Đ, Vajić U. Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films. in Journal of Drug Delivery Science and Technology. 2023;86.
doi:10.1016/j.jddst.2023.104715 .

Kurćubić, Ivana, Đuriš, Jelena, Cvijić, Sandra, Crevar, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović-Stanojević, Nevena, Karanović, Danijela, Ivanov, Milan, Jovović, Đurđica, Vajić, Una-Jovana, "Integrated in vitro – in vivo – in silico studies in the pharmaceutical development of propranolol hydrochloride mucoadhesive buccal films" in Journal of Drug Delivery Science and Technology, 86 (2023),
https://doi.org/10.1016/j.jddst.2023.104715 . .

TY  - JOUR
AU  - Krstevska, Aleksandra
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Cvijić, Sandra
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4420
AB  - In the past decade, only a small number of papers have elaborated on the application of physiologically based pharmacokinetic (PBPK) modeling across different areas. In this review, an in-depth analysis of the distribution of PBPK modeling in relation to its application in various research topics and model validation was conducted by text mining tools. Orange 3.32.0, an open-source data mining program was used for text mining. PubMed was used for data retrieval, and the collected articles were analyzed by several widgets. A total of 2699 articles related to PBPK modeling met the predefined criteria. The number of publications per year has been rising steadily. Regarding the application areas, the results revealed that 26% of the publications described the use of PBPK modeling in early drug development, risk assessment and toxicity assessment, followed by absorption/formulation modeling (25%), prediction of drug-disease interactions (20%), drug-drug interactions (DDIs) (17%) and pediatric drug development (12%). Furthermore, the analysis showed that only 12% of the publications mentioned model validation, of which 51% referred to literature-based validation and 26% to experimentally validated models. The obtained results present a valuable review of the state-of-the-art regarding PBPK modeling applications in drug discovery and development and related fields.
PB  - MDPI
T2  - Pharmaceutics
T1  - In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools
VL  - 15
IS  - 1
DO  - 10.3390/pharmaceutics15010107
ER  - 

@article{
author = "Krstevska, Aleksandra and Đuriš, Jelena and Ibrić, Svetlana and Cvijić, Sandra",
year = "2023",
abstract = "In the past decade, only a small number of papers have elaborated on the application of physiologically based pharmacokinetic (PBPK) modeling across different areas. In this review, an in-depth analysis of the distribution of PBPK modeling in relation to its application in various research topics and model validation was conducted by text mining tools. Orange 3.32.0, an open-source data mining program was used for text mining. PubMed was used for data retrieval, and the collected articles were analyzed by several widgets. A total of 2699 articles related to PBPK modeling met the predefined criteria. The number of publications per year has been rising steadily. Regarding the application areas, the results revealed that 26% of the publications described the use of PBPK modeling in early drug development, risk assessment and toxicity assessment, followed by absorption/formulation modeling (25%), prediction of drug-disease interactions (20%), drug-drug interactions (DDIs) (17%) and pediatric drug development (12%). Furthermore, the analysis showed that only 12% of the publications mentioned model validation, of which 51% referred to literature-based validation and 26% to experimentally validated models. The obtained results present a valuable review of the state-of-the-art regarding PBPK modeling applications in drug discovery and development and related fields.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools",
volume = "15",
number = "1",
doi = "10.3390/pharmaceutics15010107"
}

Krstevska, A., Đuriš, J., Ibrić, S.,& Cvijić, S.. (2023). In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools. in Pharmaceutics
MDPI., 15(1).
https://doi.org/10.3390/pharmaceutics15010107

Krstevska A, Đuriš J, Ibrić S, Cvijić S. In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools. in Pharmaceutics. 2023;15(1).
doi:10.3390/pharmaceutics15010107 .

Krstevska, Aleksandra, Đuriš, Jelena, Ibrić, Svetlana, Cvijić, Sandra, "In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools" in Pharmaceutics, 15, no. 1 (2023),
https://doi.org/10.3390/pharmaceutics15010107 . .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Petrović, Miloš
AU  - Stojanović, Dušica
AU  - Ibrić, Svetlana
AU  - Uskoković, Petar
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4410
AB  - In this work, a blend of gelatin A (GA) and polyvinylpyrrolidone (PVP K30) was used for
semi-solid 3D printing of bone scaffold for ibuprofen (IBU) delivery. The cross-linking of the
obtained scaffold was performed with a 1% glutaraldehyde (GTA) solution, followed by
lyophilization. The thermal and mechanical properties, as well as drug release profiles, and drug
kinetics of prepared scaffolds were investigated. The cross-linked and lyophilized scaffold has
shown good thermal stability, mechanical properties, and prolonged release of IBU following the
Fickian diffusion process.
AB  - Nosač za dostavu ibuprofena (IBU) u koštanom tkivu dobijen je metodom 3D štampe ekstruzijom iz paste uz korišćenje smeše polimera želatina A (GA) i polivinilpirolidona (PVP K30). Dobijeni nosač je umrežen sa 1% rastvorom glutaraldehida (GTA), nakon čega je usledio proces liofilizacije uzoraka. Ispitivana su mehanička i termička svojstva, profili i kinetika oslobađanja ibuprofena iz dobijenih nosača. Umrežen i liofilizovan nosač pokazao je dobru termičku stabilnost i mehanička svojstva, kao i produženo oslobađanje IBU-a koje prati kinetiku po Fikovom zakonu difuzije.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery
T1  - 3D štampa i karakterizacija nosača za dostavu ibuprofena u koštanom tkivu
VL  - 72
IS  - 6
SP  - 661
EP  - 673
DO  - 10.5937/arhfarm72-40262
ER  - 

@article{
author = "Jovanović, Marija and Petrović, Miloš and Stojanović, Dušica and Ibrić, Svetlana and Uskoković, Petar",
year = "2022",
abstract = "In this work, a blend of gelatin A (GA) and polyvinylpyrrolidone (PVP K30) was used for
semi-solid 3D printing of bone scaffold for ibuprofen (IBU) delivery. The cross-linking of the
obtained scaffold was performed with a 1% glutaraldehyde (GTA) solution, followed by
lyophilization. The thermal and mechanical properties, as well as drug release profiles, and drug
kinetics of prepared scaffolds were investigated. The cross-linked and lyophilized scaffold has
shown good thermal stability, mechanical properties, and prolonged release of IBU following the
Fickian diffusion process., Nosač za dostavu ibuprofena (IBU) u koštanom tkivu dobijen je metodom 3D štampe ekstruzijom iz paste uz korišćenje smeše polimera želatina A (GA) i polivinilpirolidona (PVP K30). Dobijeni nosač je umrežen sa 1% rastvorom glutaraldehida (GTA), nakon čega je usledio proces liofilizacije uzoraka. Ispitivana su mehanička i termička svojstva, profili i kinetika oslobađanja ibuprofena iz dobijenih nosača. Umrežen i liofilizovan nosač pokazao je dobru termičku stabilnost i mehanička svojstva, kao i produženo oslobađanje IBU-a koje prati kinetiku po Fikovom zakonu difuzije.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery, 3D štampa i karakterizacija nosača za dostavu ibuprofena u koštanom tkivu",
volume = "72",
number = "6",
pages = "661-673",
doi = "10.5937/arhfarm72-40262"
}

Jovanović, M., Petrović, M., Stojanović, D., Ibrić, S.,& Uskoković, P.. (2022). Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 661-673.
https://doi.org/10.5937/arhfarm72-40262

Jovanović M, Petrović M, Stojanović D, Ibrić S, Uskoković P. Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery. in Arhiv za farmaciju. 2022;72(6):661-673.
doi:10.5937/arhfarm72-40262 .

Jovanović, Marija, Petrović, Miloš, Stojanović, Dušica, Ibrić, Svetlana, Uskoković, Petar, "Preparation and characterization of 3D printed bone scaffold for ibuprofen delivery" in Arhiv za farmaciju, 72, no. 6 (2022):661-673,
https://doi.org/10.5937/arhfarm72-40262 . .

TY  - CONF
AU  - Turković, Erna
AU  - Vasiljević, Ivana
AU  - Vasiljević, Dragana
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4758
AB  - 1. INTRODUCTION
Orodispersible films (ODF) have emerged as innovative dosage forms that provide wide variety of advantages for patients and manufacturers over conventional dosage forms. The prominent characteristic of ODFs is fast disintegration followed by good patients acceptability [1]. Therefore, relevant disintegration time (DT) is usually considered as ODF critical quality attribute. Extensive research on ODFs is generating a lot of data, but lack of standardization is the main obstacle that limits their comparative evaluation. The following work aims to explore literature data on ODFs characteristics using the predictive data-classification algorithm Support vector machine (SVM) and assess its applicability in pharmaceutical development based on the set of experimentally obtained data.
2. MATERIALS AND METHODS
2.1. Materials
Hydroxypropyl cellulose (Klucel GF, Ashland, USA), ethanol (≥99.8%, Honeywell, Charlotte, NC, USA) and glycerol, 85% (w/w) (Ph. Eur.) were used for preparation of printing and casting dispersion.
2.2. Data pre-processing
Comprehensive data exploration has been conducted in the PubMed database using most common synonyms for ODFs with fifteen synonyms in singular and plural. Built database had following attributes: manufacturing approach, polymer selection, polymer molecular weight (KDa), polymer load (%), mechanical properties (tensile strength (MPa), Young's modulus (MPa), elongation at break (%)), disintegration method and disintegration time (DT) (s).
2.3. ODF preparation and characterisation
Polymer dispersions for solvent casting and semi-solid extrusion 3D printing were prepared by dispersing HPC in ethanol:glicerol solution followed by continuous stirring on the magnetic stirrer. Prepared dispersions were: (i) casted on a unit-dose plexiglas plates, or (ii) printed using Ultimaker 2+ (Ultimaker, , Netherlands). ODFs were characterized in terms of mechanical properties using Z-LX Table-Top Testing Machine (Shimadzu, Japan) and DT using adapted compendial tester (Erweka ZT52, Germany) with a weight.
3. RESULTS AND DISCUSSION
3.1. Data pre-processing
274 papers (without reviews) were identified via search, of which 112 were included in the database. Nominal data from literature was transformed into numerical, using coding operator so that each nominal data had corresponding numerical value. Critical attributes for films fast disintegration were derived. 18 polymers were included as categorical data and were further differentiated on the basis of molecular weight. Values for most commonly evaluated mechanical properties were included as numerical data. Different DT methods were classified in seven classes (Table 1), while the manufacturing methods were classified in five classes. RapidMiner Studio 9.10 (RapidMiner, Dortmund, Germany) was used to transform data and employ SMV algorithm.
3.2. SVM model prediction
Attributes with the highest weight were polymer load and DT method employed (Figure 1). The polymer type and characteristic did have conclusive effects on DT as their weight varied during data mining. This can be attributed to inconclusive data provided in papers and lot of missing values for those attributes. Mechanical properties had low weight, which can be explained with the broad value range for those attributes. Different research groups had different approach to disintegration testing, which lowered model precision as it was reported that SVM does not have high accuracy when data is imbalanced [3]. Relative error value was 20%, which can be considered as high, but, having in mind great diversity in presented data and methodology, obtained value is still acceptable for the pilot study.
3.3. Experimental validation
HPC-based films prepared by 3D printing had tensile strength, elongation at break and Young’s modulus of 3.5 MPa, 137% and 5 MPa, respectively. Average DT was 69 s. For casted films, relevant values were 3.4 MPa, 105% and 3 MPa, and DT was 27 s. Experimentally obtained results were entered into model simulator (Figure 2) to simulate situation reflecting the experimental set up in which HPC-based films were prepared by 3D printing and solvent casting, and relevant attribute values obtained by samples characterization. In the case were manufacturing method was set to be 3D printing (coded as 1) predicted DT value was close to experimentally obtained value, i.e. 71.7 and 69 s, respectively. When solvent casting method was considered, predicted DT value was remarkedly higher than the experimentally obtained one, indicating bad predictability. It might be assumed that good predictability obtained in the case of 3D printed films is associated with lower data variability due to more simple sample composition and robust preparation method. In the case of casted films, data was much more complex due to a higher number of research papers and approaches to characterisation.
4. CONCLUSION
The obtained results indicate that SVM algorithm can be employed to predict ODF DT value based on the dataset created using literature data. However, in order to obtain meaningful predictions, larger dataset, with fewer inconsistences and less missing values would be advantageous.
PB  - Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo
C3  - 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
T1  - Application of support vector machine learning for orodispersible films disintegration time prediction
SP  - 239
EP  - 240
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4758
ER  - 

@conference{
author = "Turković, Erna and Vasiljević, Ivana and Vasiljević, Dragana and Ibrić, Svetlana and Parojčić, Jelena",
year = "2022",
abstract = "1. INTRODUCTION
Orodispersible films (ODF) have emerged as innovative dosage forms that provide wide variety of advantages for patients and manufacturers over conventional dosage forms. The prominent characteristic of ODFs is fast disintegration followed by good patients acceptability [1]. Therefore, relevant disintegration time (DT) is usually considered as ODF critical quality attribute. Extensive research on ODFs is generating a lot of data, but lack of standardization is the main obstacle that limits their comparative evaluation. The following work aims to explore literature data on ODFs characteristics using the predictive data-classification algorithm Support vector machine (SVM) and assess its applicability in pharmaceutical development based on the set of experimentally obtained data.
2. MATERIALS AND METHODS
2.1. Materials
Hydroxypropyl cellulose (Klucel GF, Ashland, USA), ethanol (≥99.8%, Honeywell, Charlotte, NC, USA) and glycerol, 85% (w/w) (Ph. Eur.) were used for preparation of printing and casting dispersion.
2.2. Data pre-processing
Comprehensive data exploration has been conducted in the PubMed database using most common synonyms for ODFs with fifteen synonyms in singular and plural. Built database had following attributes: manufacturing approach, polymer selection, polymer molecular weight (KDa), polymer load (%), mechanical properties (tensile strength (MPa), Young's modulus (MPa), elongation at break (%)), disintegration method and disintegration time (DT) (s).
2.3. ODF preparation and characterisation
Polymer dispersions for solvent casting and semi-solid extrusion 3D printing were prepared by dispersing HPC in ethanol:glicerol solution followed by continuous stirring on the magnetic stirrer. Prepared dispersions were: (i) casted on a unit-dose plexiglas plates, or (ii) printed using Ultimaker 2+ (Ultimaker, , Netherlands). ODFs were characterized in terms of mechanical properties using Z-LX Table-Top Testing Machine (Shimadzu, Japan) and DT using adapted compendial tester (Erweka ZT52, Germany) with a weight.
3. RESULTS AND DISCUSSION
3.1. Data pre-processing
274 papers (without reviews) were identified via search, of which 112 were included in the database. Nominal data from literature was transformed into numerical, using coding operator so that each nominal data had corresponding numerical value. Critical attributes for films fast disintegration were derived. 18 polymers were included as categorical data and were further differentiated on the basis of molecular weight. Values for most commonly evaluated mechanical properties were included as numerical data. Different DT methods were classified in seven classes (Table 1), while the manufacturing methods were classified in five classes. RapidMiner Studio 9.10 (RapidMiner, Dortmund, Germany) was used to transform data and employ SMV algorithm.
3.2. SVM model prediction
Attributes with the highest weight were polymer load and DT method employed (Figure 1). The polymer type and characteristic did have conclusive effects on DT as their weight varied during data mining. This can be attributed to inconclusive data provided in papers and lot of missing values for those attributes. Mechanical properties had low weight, which can be explained with the broad value range for those attributes. Different research groups had different approach to disintegration testing, which lowered model precision as it was reported that SVM does not have high accuracy when data is imbalanced [3]. Relative error value was 20%, which can be considered as high, but, having in mind great diversity in presented data and methodology, obtained value is still acceptable for the pilot study.
3.3. Experimental validation
HPC-based films prepared by 3D printing had tensile strength, elongation at break and Young’s modulus of 3.5 MPa, 137% and 5 MPa, respectively. Average DT was 69 s. For casted films, relevant values were 3.4 MPa, 105% and 3 MPa, and DT was 27 s. Experimentally obtained results were entered into model simulator (Figure 2) to simulate situation reflecting the experimental set up in which HPC-based films were prepared by 3D printing and solvent casting, and relevant attribute values obtained by samples characterization. In the case were manufacturing method was set to be 3D printing (coded as 1) predicted DT value was close to experimentally obtained value, i.e. 71.7 and 69 s, respectively. When solvent casting method was considered, predicted DT value was remarkedly higher than the experimentally obtained one, indicating bad predictability. It might be assumed that good predictability obtained in the case of 3D printed films is associated with lower data variability due to more simple sample composition and robust preparation method. In the case of casted films, data was much more complex due to a higher number of research papers and approaches to characterisation.
4. CONCLUSION
The obtained results indicate that SVM algorithm can be employed to predict ODF DT value based on the dataset created using literature data. However, in order to obtain meaningful predictions, larger dataset, with fewer inconsistences and less missing values would be advantageous.",
publisher = "Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo",
journal = "9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts",
title = "Application of support vector machine learning for orodispersible films disintegration time prediction",
pages = "239-240",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4758"
}

Turković, E., Vasiljević, I., Vasiljević, D., Ibrić, S.,& Parojčić, J.. (2022). Application of support vector machine learning for orodispersible films disintegration time prediction. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo., 239-240.
https://hdl.handle.net/21.15107/rcub_farfar_4758

Turković E, Vasiljević I, Vasiljević D, Ibrić S, Parojčić J. Application of support vector machine learning for orodispersible films disintegration time prediction. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts. 2022;:239-240.
https://hdl.handle.net/21.15107/rcub_farfar_4758 .

Turković, Erna, Vasiljević, Ivana, Vasiljević, Dragana, Ibrić, Svetlana, Parojčić, Jelena, "Application of support vector machine learning for orodispersible films disintegration time prediction" in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts (2022):239-240,
https://hdl.handle.net/21.15107/rcub_farfar_4758 .

TY  - JOUR
AU  - Nikolić, Nenad
AU  - Miletić, Tijana
AU  - Kovačević, Jovana
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4407
AB  - Compaction simulators are designed as machines which can provide an in-depth analysis
of the powder compaction process. Characterization of the powder compression and compaction
process, as well as material characterization, play an important role in the formulation and
manufacturing process design and development, as well as in creating a strong knowledge basis
for the scale-up of the tablet compression and troubleshooting in further stages of the product
lifecycle. Although compaction simulators are designed to simulate the compression process on
high-speed tablet-presses, with the advantages of a small quantity of material needed and highly
sophisticated instrumentation, there are certain limitations in the extrapolation of the process
parameters from these machines to high-speed rotary tablet presses. However, the advantage of
the use of compaction simulators for studying basic compression and compaction mechanisms,
identification of critical material attributes and critical process parameters ranges, and their
relations with tablet characteristics and critical quality attributes of pharmaceutical products is
clear, compared to the use of small excentre tablet presses, and complementary to the use of small
rotary tablet presses.
This scientific paper provides an overview and examples of the different advantages
provided by the instrumentation of compaction simulators, including certain limitations in their
exploitation.
AB  - Simulatori kompaktiranja su uređaji dizajnirani da omoguće dublju analizu procesa komprimovanja praškova. Karakterizacija procesa kompresije i kompakcije praškova, kao i karakterizacija materijala, ima važnu ulogu u dizajnu i razvoju formulacije i proizvodnog procesa tableta, kao i za kreiranje snažne baze za transfer proizvodnog procesa komprimovanja tableta na proizvodnu opremu i rešavanje problema u proizvodnim procesima u kasnijim fazama životnog ciklusa proizvoda. Iako su simulatori kompaktiranja dizajnirani da simuliraju proces kompresije na tablet-presama visoke brzine, obezbeđujući prednost korišćenja manjih količina materijala i visoko sofisticirane instrumentacije, postoje određena ograničenja u ekstrapolaciji procesnih parametara sa ovih mašina na tablet-prese visokih brzina. Međutim, prednosti upotrebe simulatora kompaktiranja za proučavanje osnovnih mehanizama kompresije i kompaktiranja, identifikaciju kritičnih karakteristika materijala i opsega kritičnih procesnih parametara, kao i njihovih relacija sa karakteristikama tableta, i kritičnim karakteristikama farmaceutskih proizvoda su očigledne, u poređenju sa korišćenjem malih ekscenter tablet presa, i komplementarne sa upotrebom manjih rotacionih tablet presa. U ovom radu je prikazan pregled i primeri različitih prednosti omogućenih nivoom instrumentacije simulatora kompaktiranja, uključujući i ograničenja u njihovoj eksploataciji.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Usage of compaction simulators for the powder compression characterization – advantages and limitations
T1  - Upotreba simulatora kompaktiranja za karakterizaciju kompresije praškova - prednosti i ograničenja
VL  - 72
IS  - 6
SP  - 546
EP  - 565
DO  - 10.5937/arhfarm72-41301
ER  - 

@article{
author = "Nikolić, Nenad and Miletić, Tijana and Kovačević, Jovana and Medarević, Đorđe and Ibrić, Svetlana",
year = "2022",
abstract = "Compaction simulators are designed as machines which can provide an in-depth analysis
of the powder compaction process. Characterization of the powder compression and compaction
process, as well as material characterization, play an important role in the formulation and
manufacturing process design and development, as well as in creating a strong knowledge basis
for the scale-up of the tablet compression and troubleshooting in further stages of the product
lifecycle. Although compaction simulators are designed to simulate the compression process on
high-speed tablet-presses, with the advantages of a small quantity of material needed and highly
sophisticated instrumentation, there are certain limitations in the extrapolation of the process
parameters from these machines to high-speed rotary tablet presses. However, the advantage of
the use of compaction simulators for studying basic compression and compaction mechanisms,
identification of critical material attributes and critical process parameters ranges, and their
relations with tablet characteristics and critical quality attributes of pharmaceutical products is
clear, compared to the use of small excentre tablet presses, and complementary to the use of small
rotary tablet presses.
This scientific paper provides an overview and examples of the different advantages
provided by the instrumentation of compaction simulators, including certain limitations in their
exploitation., Simulatori kompaktiranja su uređaji dizajnirani da omoguće dublju analizu procesa komprimovanja praškova. Karakterizacija procesa kompresije i kompakcije praškova, kao i karakterizacija materijala, ima važnu ulogu u dizajnu i razvoju formulacije i proizvodnog procesa tableta, kao i za kreiranje snažne baze za transfer proizvodnog procesa komprimovanja tableta na proizvodnu opremu i rešavanje problema u proizvodnim procesima u kasnijim fazama životnog ciklusa proizvoda. Iako su simulatori kompaktiranja dizajnirani da simuliraju proces kompresije na tablet-presama visoke brzine, obezbeđujući prednost korišćenja manjih količina materijala i visoko sofisticirane instrumentacije, postoje određena ograničenja u ekstrapolaciji procesnih parametara sa ovih mašina na tablet-prese visokih brzina. Međutim, prednosti upotrebe simulatora kompaktiranja za proučavanje osnovnih mehanizama kompresije i kompaktiranja, identifikaciju kritičnih karakteristika materijala i opsega kritičnih procesnih parametara, kao i njihovih relacija sa karakteristikama tableta, i kritičnim karakteristikama farmaceutskih proizvoda su očigledne, u poređenju sa korišćenjem malih ekscenter tablet presa, i komplementarne sa upotrebom manjih rotacionih tablet presa. U ovom radu je prikazan pregled i primeri različitih prednosti omogućenih nivoom instrumentacije simulatora kompaktiranja, uključujući i ograničenja u njihovoj eksploataciji.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Usage of compaction simulators for the powder compression characterization – advantages and limitations, Upotreba simulatora kompaktiranja za karakterizaciju kompresije praškova - prednosti i ograničenja",
volume = "72",
number = "6",
pages = "546-565",
doi = "10.5937/arhfarm72-41301"
}

Nikolić, N., Miletić, T., Kovačević, J., Medarević, Đ.,& Ibrić, S.. (2022). Usage of compaction simulators for the powder compression characterization – advantages and limitations. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 546-565.
https://doi.org/10.5937/arhfarm72-41301

Nikolić N, Miletić T, Kovačević J, Medarević Đ, Ibrić S. Usage of compaction simulators for the powder compression characterization – advantages and limitations. in Arhiv za farmaciju. 2022;72(6):546-565.
doi:10.5937/arhfarm72-41301 .

Nikolić, Nenad, Miletić, Tijana, Kovačević, Jovana, Medarević, Đorđe, Ibrić, Svetlana, "Usage of compaction simulators for the powder compression characterization – advantages and limitations" in Arhiv za farmaciju, 72, no. 6 (2022):546-565,
https://doi.org/10.5937/arhfarm72-41301 . .

TY  - JOUR
AU  - Adamov, Ivana
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Ivković, Aleksandar
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4411
AB  - Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release.
AB  - Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill
T1  - 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule
VL  - 72
IS  - 6
SP  - 674
EP  - 688
DO  - 10.5937/arhfarm72-40365
ER  - 

@article{
author = "Adamov, Ivana and Medarević, Đorđe and Ivković, Branka and Ivković, Aleksandar and Ibrić, Svetlana",
year = "2022",
abstract = "Ever since 3D printing was introduced to the field of pharmacy, it has caused a paradigm
shift from the manufacturing of large-scale to small batches of medicines tailored accordingly to
the specific needs of patients. This study aimed to formulate and fabricate two-layered 3D tablets
using the digital light processing (DLP) technique. Hydrochlorothiazide (HHT,5%,w/w) and
warfarin sodium (WS,5%,w/w) were selected as model drugs. The printing process was initiated
with 0.1% of photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and
poly(ethylene glycol) 400, 1:1, with the addition of water (10%,w/w). Single-layered tablets of
8.00 mm diameter and 1.50 mm thickness, containing HHT and WS respectively, were
successfully printed, as well as combined two-layered 3D tablets, with each of the active
substances in separate layers. Dissolution tests of single-layered tablets showed immediate, but
incomplete release of WS (81.47±1.47%, after 45min), and prolonged and complete release of
HHT (98.17±3.11%, after 8h), while significantly slower and incomplete release of both drugs
from the combined two-layered 3D tablets was observed. The absence of drug-polymer
interaction and presence of a layered cross-sectional tablet structure were confirmed. DLP
technique enables simple and rapid fabrication of combined two-layered 3D tablets, while further
optimization of formulation factors is necessary to achieve complete drug release., Uvođenje tehnologije 3D štampe u oblasti farmacije uslovilo je razvoj fundamentalnih promena, pri čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama lekova prilagođenih prema specifičnim potrebama pacijenata. Cilj istraživanja bio je da se formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP). Hidrohlortiazid (HHT, 5%, m/m) i varfarin-natrijum (WS, 5%, m/m) odabrani su kao model lekovite supstance. Proces štampanja sproveden je u prisustvu 0,1% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. Jednoslojne 3D tablete prečnika 8,00 mm i debljine 1,50 mm, koje sadrže HHT, odnosno WS, kao i kombinovane dvoslojne 3D tablete, sa svakom od aktivnih supstanci u posebnom sloju, uspešno su odštampane. Prilikom ispitivanja brzine rastvaranja lekovite supstance iz jednoslojnih tableta, došlo je do trenutnog (81,47±1,47%, nakon 45 min), ali nepotpunog oslobađanja WS, i produženog i potpunog oslobađanja HHT (98,17±3,11%, nakon 8 h), dok je iz kombinovanih tableta zapaženo znatno sporije i nepotpuno oslobađanje obe lekovite supstance. Potvrđeno je odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika pruža mogućnost jednostavne i brze izrade kombinovanih tableta, pri čemu je dalja optimizacija formulacionih faktora neophodna u cilju postizanja potpunog oslobađanja lekovite supstance.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill, 3D tehnika digitalne obrade svetlosti (DLP) primenjena u izradi dvoslojnih tableta: koncept kombinovane polipilule",
volume = "72",
number = "6",
pages = "674-688",
doi = "10.5937/arhfarm72-40365"
}

Adamov, I., Medarević, Đ., Ivković, B., Ivković, A.,& Ibrić, S.. (2022). Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 674-688.
https://doi.org/10.5937/arhfarm72-40365

Adamov I, Medarević Đ, Ivković B, Ivković A, Ibrić S. Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill. in Arhiv za farmaciju. 2022;72(6):674-688.
doi:10.5937/arhfarm72-40365 .

Adamov, Ivana, Medarević, Đorđe, Ivković, Branka, Ivković, Aleksandar, Ibrić, Svetlana, "Digital light processing (DLP) 3D printing technique applied in the fabrication of two-layered tablets: the concept of a combined polypill" in Arhiv za farmaciju, 72, no. 6 (2022):674-688,
https://doi.org/10.5937/arhfarm72-40365 . .

TY  - JOUR
AU  - Kovačević, Jovana
AU  - Kovačević, Aleksandar
AU  - Miletić, Tijana
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4413
AB  - Understanding the effect of the characteristics of formulation and process parameters on
the physicochemical properties of a pharmaceutical product is very significant for the
development of solid dosage forms, as the knowledge gained on small scale batches in the early
phase of development is used in the later phases of product lifecycle or in the development of
other products. One of the approaches for gaining a better understanding of the effects of the
formulation and production process on the quality of the finished product is to apply a
systematical approach which concerns performing experiments according to a predefined factorial
or fractional factorial experimental plan. However, often it is the case that there are available data
gathered in a non-systematic way, because experiments were not performed according to a
predetermined experimental plan. In such a case, data mining techniques could be used to extract
useful data from the historical data set. In this research, the possibility of using several data mining
techniques to build models that describe the effect of formulation characteristics on acid resistance
and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the
research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2
class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of
duloxetine to be characterized by a higher number of tested time points. The developed models
can be used for planning future laboratory trials, or in the development of other products.
AB  - Razumevanje uticaja karakteristika formulacije i procesnih parametara na fizičkohemijske osobine farmaceutskog proizvoda je vrlo značajno u razvoju čvrstih doziranih oblika jer se znanje stečeno u fazi razvoja koristi i u svim sledećim fazama životnog ciklusa proizvoda, a može da se primeni i u razvoju drugih proizvoda. Jedan pristup ka postizanju boljeg poznavanja proizvoda i procesa je primena sistematičnog pristupa koji podrazumeva izvođenje eksperimenata u skladu sa predefinisanim faktorijalnim ili frakcionim faktorijalnim eksperiementalnim planom. Međutim, čest je slučaj da dostupni podaci nisu prikupljeni na sistematičan način zato što eksperimenti nisu izvođeni po predefinisanom planu. Tada se mogu primeniti tehnike istraživanja i analize podataka da bi se iz seta istorijskih podataka izdvojili korisni podaci. U ovom istraživanju smo ispitali mogućnost korišćenja različitih tehnika istraživanja i analize podataka za razvoj modela koji opisuju efekte formulacije na gastrorezistenciju i profil oslobađanja model supstance iz gastrorezistentnih peleta. Model supstanca je duloksetin hidrohlorid iz grupe antidepresiva. Pripada BCS 2 klasi lekovitih supstanci, te je poželjno da profil brzine rastvaranja duloksetina iz peleta bude okarakterisan većim brojem vremenskih tačaka. Razvijeni modeli se mogu koristiti za planiranje narednih proba ili u razvoju drugih proizvoda.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Data mining techniques applied in the analysis of historical data
T1  - Tehnika istraživanja i analize podataka primenjena u analizi istorijskih podataka
VL  - 72
IS  - 6
SP  - 701
EP  - 715
DO  - 10.5937/arhfarm72-41368
ER  - 

@article{
author = "Kovačević, Jovana and Kovačević, Aleksandar and Miletić, Tijana and Đuriš, Jelena and Ibrić, Svetlana",
year = "2022",
abstract = "Understanding the effect of the characteristics of formulation and process parameters on
the physicochemical properties of a pharmaceutical product is very significant for the
development of solid dosage forms, as the knowledge gained on small scale batches in the early
phase of development is used in the later phases of product lifecycle or in the development of
other products. One of the approaches for gaining a better understanding of the effects of the
formulation and production process on the quality of the finished product is to apply a
systematical approach which concerns performing experiments according to a predefined factorial
or fractional factorial experimental plan. However, often it is the case that there are available data
gathered in a non-systematic way, because experiments were not performed according to a
predetermined experimental plan. In such a case, data mining techniques could be used to extract
useful data from the historical data set. In this research, the possibility of using several data mining
techniques to build models that describe the effect of formulation characteristics on acid resistance
and dissolution profile of a model drug from gastro-resistant pellets. The model drug used in the
research is duloxetine hydrochloride from the group of antidepressants. It belongs to the BCS 2
class of active pharmaceutical ingredients, and it is therefore necessary for the release profile of
duloxetine to be characterized by a higher number of tested time points. The developed models
can be used for planning future laboratory trials, or in the development of other products., Razumevanje uticaja karakteristika formulacije i procesnih parametara na fizičkohemijske osobine farmaceutskog proizvoda je vrlo značajno u razvoju čvrstih doziranih oblika jer se znanje stečeno u fazi razvoja koristi i u svim sledećim fazama životnog ciklusa proizvoda, a može da se primeni i u razvoju drugih proizvoda. Jedan pristup ka postizanju boljeg poznavanja proizvoda i procesa je primena sistematičnog pristupa koji podrazumeva izvođenje eksperimenata u skladu sa predefinisanim faktorijalnim ili frakcionim faktorijalnim eksperiementalnim planom. Međutim, čest je slučaj da dostupni podaci nisu prikupljeni na sistematičan način zato što eksperimenti nisu izvođeni po predefinisanom planu. Tada se mogu primeniti tehnike istraživanja i analize podataka da bi se iz seta istorijskih podataka izdvojili korisni podaci. U ovom istraživanju smo ispitali mogućnost korišćenja različitih tehnika istraživanja i analize podataka za razvoj modela koji opisuju efekte formulacije na gastrorezistenciju i profil oslobađanja model supstance iz gastrorezistentnih peleta. Model supstanca je duloksetin hidrohlorid iz grupe antidepresiva. Pripada BCS 2 klasi lekovitih supstanci, te je poželjno da profil brzine rastvaranja duloksetina iz peleta bude okarakterisan većim brojem vremenskih tačaka. Razvijeni modeli se mogu koristiti za planiranje narednih proba ili u razvoju drugih proizvoda.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Data mining techniques applied in the analysis of historical data, Tehnika istraživanja i analize podataka primenjena u analizi istorijskih podataka",
volume = "72",
number = "6",
pages = "701-715",
doi = "10.5937/arhfarm72-41368"
}

Kovačević, J., Kovačević, A., Miletić, T., Đuriš, J.,& Ibrić, S.. (2022). Data mining techniques applied in the analysis of historical data. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 701-715.
https://doi.org/10.5937/arhfarm72-41368

Kovačević J, Kovačević A, Miletić T, Đuriš J, Ibrić S. Data mining techniques applied in the analysis of historical data. in Arhiv za farmaciju. 2022;72(6):701-715.
doi:10.5937/arhfarm72-41368 .

Kovačević, Jovana, Kovačević, Aleksandar, Miletić, Tijana, Đuriš, Jelena, Ibrić, Svetlana, "Data mining techniques applied in the analysis of historical data" in Arhiv za farmaciju, 72, no. 6 (2022):701-715,
https://doi.org/10.5937/arhfarm72-41368 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Pilović, Jovana
AU  - Džunić, Marina
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4412
AB  - Text mining (TM) applications in the field of biomedicine are gaining great interest. TM
tools can facilitate formulation development by analyzing textual information from patent
databases, scientific articles, summary of products characteristics, etc. The aim of this study was
to utilize TM tools to perform qualitative analysis of paracetamol (PAR) and ibuprofen (IBU)
formulations, in terms of identifying and evaluating the presence of excipients specific to the
active pharmaceutical ingredient (API) and/or dosage form. A total of 152 products were
analyzed. Web-scraping was used to retrieve the data, and Python-based open-source software
Orange 3.31.1 was used for TM and statistical analysis (ANOVA) of the obtained results. The
majority of marketed products for both APIs were tablets. The predominant excipients in all tablet
formulations were povidone, starch, microcrystalline cellulose and hypromellose. Povidone,
stearic acid, potassium sorbate, maize starch and pregelatinized starch occurred more frequently
in PAR tablets. On the other hand, titanium dioxide, lactose, shellac, sucrose and ammonium
hydroxide were specific to IBU tablets. PAR oral suspensions more frequently contained
dispersible cellulose; liquid sorbitol; methyl and propyl parahydroxybenzoate, glycerol and
acesulfame potassium. Specific excipients in other PAR dosage forms, such as effervescent
tablets, hard capsules, oral powders, solutions and suspensions, as well as IBU gels and soft
capsules, were also evaluated.
AB  - Primena text mining (TM) alata u oblasti biomedicine postaje sve značajnija. TM alati mogu da olakšaju razvoj formulacija, tako što omogućavaju analizu tekstualnih informacija iz patentnih baza, naučnih članaka, sažetaka karakteristika lekova, itd. Cilj ovog rada bila je primena TM alata za kvalitativnu analizu formulacija paracetamola (PAR) i ibuprofena (IBU), u smislu identifikacije i procene prisustva ekscipijenasa koji su karakteristični za lekovitu supstancu i/ili farmaceutski oblik. Ukupno je analiziran sastav 152 preparata. Web-scraping je primenjen za prikupljanje podataka, a Orange 3.31.1, softver otvorenog koda zasnovan na programskom jeziku Python, primenjen je za TM i statističku analizu (ANOVA) dobijenih rezultata. Većina analiziranih formulacija za obe lekovite supstance bile su tablete, a najzastupljeniji ekscipijensi u njima su bili povidon, skrob, mikrokristalna celuloza i hipromeloza. Povidon, stearinska kiselina, kalijum sorbat, kukuruzni skrob i pregelirani skrob se češće pronalaze u formulacijama PAR tableta. Titanijum-dioksid, laktoza, šelak, saharoza i amonijum hidroksid su specifični za IBU tablete. PAR peroralne suspenzije su češće sadržale disperzibilnu celulozu; tečni sorbitol; metil-i propil parahidroksibenzoat, glicerol i acesulfam-kalijum. Takođe su identifikovani i specifični ekscipijensi za PAR efervescentne tablete, tvrde kapsule, peroralne praškove, rastvore i suspenzije, kao i za IBU gelove i meke kapsule.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products’ qualitative composition
T1  - Primena tehnika za sistematizovanu obradu tekstualnih informacija u cilju analize kvalitativnog sastava registrovanih preparata paracetamola i ibuprofena
VL  - 72
IS  - 6
SP  - 689
EP  - 700
DO  - 10.5937/arhfarm72-40397
ER  - 

@article{
author = "Đuriš, Jelena and Pilović, Jovana and Džunić, Marina and Cvijić, Sandra and Ibrić, Svetlana",
year = "2022",
abstract = "Text mining (TM) applications in the field of biomedicine are gaining great interest. TM
tools can facilitate formulation development by analyzing textual information from patent
databases, scientific articles, summary of products characteristics, etc. The aim of this study was
to utilize TM tools to perform qualitative analysis of paracetamol (PAR) and ibuprofen (IBU)
formulations, in terms of identifying and evaluating the presence of excipients specific to the
active pharmaceutical ingredient (API) and/or dosage form. A total of 152 products were
analyzed. Web-scraping was used to retrieve the data, and Python-based open-source software
Orange 3.31.1 was used for TM and statistical analysis (ANOVA) of the obtained results. The
majority of marketed products for both APIs were tablets. The predominant excipients in all tablet
formulations were povidone, starch, microcrystalline cellulose and hypromellose. Povidone,
stearic acid, potassium sorbate, maize starch and pregelatinized starch occurred more frequently
in PAR tablets. On the other hand, titanium dioxide, lactose, shellac, sucrose and ammonium
hydroxide were specific to IBU tablets. PAR oral suspensions more frequently contained
dispersible cellulose; liquid sorbitol; methyl and propyl parahydroxybenzoate, glycerol and
acesulfame potassium. Specific excipients in other PAR dosage forms, such as effervescent
tablets, hard capsules, oral powders, solutions and suspensions, as well as IBU gels and soft
capsules, were also evaluated., Primena text mining (TM) alata u oblasti biomedicine postaje sve značajnija. TM alati mogu da olakšaju razvoj formulacija, tako što omogućavaju analizu tekstualnih informacija iz patentnih baza, naučnih članaka, sažetaka karakteristika lekova, itd. Cilj ovog rada bila je primena TM alata za kvalitativnu analizu formulacija paracetamola (PAR) i ibuprofena (IBU), u smislu identifikacije i procene prisustva ekscipijenasa koji su karakteristični za lekovitu supstancu i/ili farmaceutski oblik. Ukupno je analiziran sastav 152 preparata. Web-scraping je primenjen za prikupljanje podataka, a Orange 3.31.1, softver otvorenog koda zasnovan na programskom jeziku Python, primenjen je za TM i statističku analizu (ANOVA) dobijenih rezultata. Većina analiziranih formulacija za obe lekovite supstance bile su tablete, a najzastupljeniji ekscipijensi u njima su bili povidon, skrob, mikrokristalna celuloza i hipromeloza. Povidon, stearinska kiselina, kalijum sorbat, kukuruzni skrob i pregelirani skrob se češće pronalaze u formulacijama PAR tableta. Titanijum-dioksid, laktoza, šelak, saharoza i amonijum hidroksid su specifični za IBU tablete. PAR peroralne suspenzije su češće sadržale disperzibilnu celulozu; tečni sorbitol; metil-i propil parahidroksibenzoat, glicerol i acesulfam-kalijum. Takođe su identifikovani i specifični ekscipijensi za PAR efervescentne tablete, tvrde kapsule, peroralne praškove, rastvore i suspenzije, kao i za IBU gelove i meke kapsule.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products’ qualitative composition, Primena tehnika za sistematizovanu obradu tekstualnih informacija u cilju analize kvalitativnog sastava registrovanih preparata paracetamola i ibuprofena",
volume = "72",
number = "6",
pages = "689-700",
doi = "10.5937/arhfarm72-40397"
}

Đuriš, J., Pilović, J., Džunić, M., Cvijić, S.,& Ibrić, S.. (2022). Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products’ qualitative composition. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 72(6), 689-700.
https://doi.org/10.5937/arhfarm72-40397

Đuriš J, Pilović J, Džunić M, Cvijić S, Ibrić S. Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products’ qualitative composition. in Arhiv za farmaciju. 2022;72(6):689-700.
doi:10.5937/arhfarm72-40397 .

Đuriš, Jelena, Pilović, Jovana, Džunić, Marina, Cvijić, Sandra, Ibrić, Svetlana, "Application of text-mining techniques for extraction and analysis of paracetamol and ibuprofen marketed products’ qualitative composition" in Arhiv za farmaciju, 72, no. 6 (2022):689-700,
https://doi.org/10.5937/arhfarm72-40397 . .

TY  - JOUR
AU  - Šušteršič, Tijana
AU  - Bodić, Aleksandar
AU  - Ignjatović, Jelisaveta
AU  - Cvijić, Sandra
AU  - Ibrić, Svetlana
AU  - Filipović, Nenad
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4367
AB  - The development of novel dry powders for dry powder inhalers (DPIs) requires the in vitro assessment of DPI aerodynamic performance. As a potential complementary method, in silico numerical simulations can provide additional information about the mechanisms that guide the particles and their behavior inside DPIs. The aim of this study was to apply computational fluid dynamics (CFDs) coupled with a discrete phase model (DPM) to describe the forces and particle trajectories inside the RS01® as a model DPI device. The methodology included standard fluid flow equations but also additional equations for the particle sticking mechanism, as well as particle behavior after contacting the DPI wall surface, including the particle detachment process. The results show that the coefficient of restitution between the particle and the impact surface does not have a high impact on the results, meaning that all tested combinations gave similar output efficiencies and particle behaviors. No sliding or rolling mechanisms were observed for the particle detachment process, meaning that simple bouncing off or deposition particle behavior is present inside DPIs. The developed methodology can serve as a basis for the additional understanding of the particles’ behavior inside DPIs, which is not possible using only in vitro experiments; this implies the possibility of increasing the efficiency of DPIs.
PB  - MDPI
T2  - Pharmaceutics
T1  - Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler
VL  - 14
IS  - 12
DO  - 10.3390/pharmaceutics14122591
ER  - 

@article{
author = "Šušteršič, Tijana and Bodić, Aleksandar and Ignjatović, Jelisaveta and Cvijić, Sandra and Ibrić, Svetlana and Filipović, Nenad",
year = "2022",
abstract = "The development of novel dry powders for dry powder inhalers (DPIs) requires the in vitro assessment of DPI aerodynamic performance. As a potential complementary method, in silico numerical simulations can provide additional information about the mechanisms that guide the particles and their behavior inside DPIs. The aim of this study was to apply computational fluid dynamics (CFDs) coupled with a discrete phase model (DPM) to describe the forces and particle trajectories inside the RS01® as a model DPI device. The methodology included standard fluid flow equations but also additional equations for the particle sticking mechanism, as well as particle behavior after contacting the DPI wall surface, including the particle detachment process. The results show that the coefficient of restitution between the particle and the impact surface does not have a high impact on the results, meaning that all tested combinations gave similar output efficiencies and particle behaviors. No sliding or rolling mechanisms were observed for the particle detachment process, meaning that simple bouncing off or deposition particle behavior is present inside DPIs. The developed methodology can serve as a basis for the additional understanding of the particles’ behavior inside DPIs, which is not possible using only in vitro experiments; this implies the possibility of increasing the efficiency of DPIs.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler",
volume = "14",
number = "12",
doi = "10.3390/pharmaceutics14122591"
}

Šušteršič, T., Bodić, A., Ignjatović, J., Cvijić, S., Ibrić, S.,& Filipović, N.. (2022). Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler. in Pharmaceutics
MDPI., 14(12).
https://doi.org/10.3390/pharmaceutics14122591

Šušteršič T, Bodić A, Ignjatović J, Cvijić S, Ibrić S, Filipović N. Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler. in Pharmaceutics. 2022;14(12).
doi:10.3390/pharmaceutics14122591 .

Šušteršič, Tijana, Bodić, Aleksandar, Ignjatović, Jelisaveta, Cvijić, Sandra, Ibrić, Svetlana, Filipović, Nenad, "Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler" in Pharmaceutics, 14, no. 12 (2022),
https://doi.org/10.3390/pharmaceutics14122591 . .

TY  - CONF
AU  - Kurćubić, Ivana
AU  - Vajić, Una‐Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Ibrić, Svetlana
AU  - Miloradović, Zoran
AU  - Mihailović‐Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4512
AB  - Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect.
AB  - Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension
T1  - Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije
VL  - 72
IS  - 4 suplement
SP  - S235
EP  - S236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4512
ER  - 

@conference{
author = "Kurćubić, Ivana and Vajić, Una‐Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Ibrić, Svetlana and Miloradović, Zoran and Mihailović‐Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2022",
abstract = "Mucoadhesive buccal films can improve drug absorption by prolonging its retention
time on the buccal mucosa (1). The aim of the study was a comparative assessment of the
hemodynamic effects and pharmacokinetics of propranolol hydrochloride (PROP) after
buccal and oral administration in spontaneously hypertensive rats. Animals were divided
into 3 groups: Group I (control) received 0.5 mL of water with a gastric tube, group II
received an immediate-release 10 mg PROP tablet via gastric tube, and group III received a
mucoadhesive 10 mg PROP buccal film. Systolic (SP) and diastolic blood pressure (DP), and
heart rate (SF) were measured in rats, and pharmacokinetic PROP parameters, Cmax, tmax,
and AUC0 → 24, were calculated by noncompartmental analysis. Mucoadhesive buccal films
showed superior degree of absorption of PROP over immediate-release tablets (AUC0 → 24:
69.64 μgh/ml versus 24.61 μgh/ml). The tmax value was significantly higher in
mucoadhesive buccal films, which indicates a prolonged PROP release and longer
therapeutic effect (71.19h versus 29.73h). There was no statistically significant difference in
Cmax values between groups II and III of rats (4.74 μg ml versus 7.11 μg ml). Mucoadhesive
buccal films provide a more pronounced and long-lasting reduction primarily of SF
(reduction of 28-51% lasting from 10 minutes to the twelfth hour of testing), but also SP and
DP (between 15-30% from the first to the sixth hour of testing) compared to immediate-
release tablets. Mucoadhesive buccal films allow bypass/reduction of the extensive hepatic
first-pass metabolism, and consequently improve the therapeutic PROP effect., Mukoadhezivni bukalni filmovi mogu poboljšati apsorpciju lekovite supstance
produžavajuć i vreme zadržavanja lekovitog preparata na bukalnoj sluznici (1). Cilj studije je
bila komparativna procena hemodinamskih efekata i farmakokinetike propranolol-
hidrohlorida (PROP) nakon bukalne i peroralne primene kod sponatano hipertenzivnih
pacova. Spontano hipertenzivni pacovi su podeljeni u 3 grupe: I (kontrolna) grupa je dobila
0,5 mL vode gastričnom sondom, II grupa je dobila tabletu sa trenutnim oslobađanjem sa 10
mg PROP gastričnom sondom i III grupa je dobila mukoadhezivni bukalni film sa 10 mg
PROP. Filmovi su pripremljeni korišćenjem polietilenoksida, hidroksipropilmetilceluloze i
polivinilalkohola kao film-formirajućih polimera sa mukoadhezivnim svojstvima. Pacovima
su mereni sistolni (SP) i dijastolni krvni pritisak (DP), srčana frekvencija (SF), a
neprostornom farmakokinetičkom analizom izračunati su parametri PROP: Cmax, t max i
AUC0→24 . Mukoadhezivni bukalni filmovi su pokazali superiornost u odnosu na tablete sa
trenutnim oslobađanjem u pogledu stepena apsorpcije PROP (AUC 0→24 : 69,64 μgh/ml
naspram 24,61 μgh/ml). Tmax vrednost je bila značajno veća kod mukoadhezivnih bukalnih
filmova što ukazuje na produženo oslobađanje PROP i duži terapijski efekat (71,19 h
naspram 29,73 h). Između II i II grupe pacova nema statistički značajne razlike u
vrednostima Cmax (4,74 μg/ml naspram 7,11 μg/ml). Mukoadhezivni bukalni filmovi izazivaju
izraženije i dugotrajnije smanjenje pre svega SF (smanjenje od 28-51% u trajanju od 10
minuta do dvanaestog sata ispitivanja), ali i SP i DP (između 15-30% od prvog do šestog sata
ispitivanja) u odnosu na tablete sa trenutnim oslobađanjem. Pripremljeni mukoadhezivni
bukalni filmovi omogućavaju zaobilazak/smanjenje ekstenzivnog metabolizma prvog
prolaza kroz jetru i posledično poboljšavaju terapijski efekat PROP.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension, Efekti akutne primene mukoadhezivnih bukalnih filmova sa propranolol‐hidrohloridom u animalnom modelu esencijalne hipertenzije",
volume = "72",
number = "4 suplement",
pages = "S235-S236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4512"
}

Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Ibrić, S., Miloradović, Z., Mihailović‐Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2022). Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512

Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Ibrić S, Miloradović Z, Mihailović‐Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension. in Arhiv za farmaciju. 2022;72(4 suplement):S235-S236.
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

Kurćubić, Ivana, Vajić, Una‐Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Ibrić, Svetlana, Miloradović, Zoran, Mihailović‐Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Effects of acute application of mucoadhesive buccal films with propranolol hydrochloride in an animal model of essential hypertension" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S235-S236,
https://hdl.handle.net/21.15107/rcub_farfar_4512 .

TY  - CONF
AU  - Pešić, Nikola
AU  - Krkobabić, Mirjana
AU  - Adamov, Ivana
AU  - Ibrić, Svetlana
AU  - Ivković, Branka
AU  - Medarević, Đorđe
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4749
AB  - 1. INTRODUCTION
When it comes to pharmacy, 3D printing has
gained immense popularity in recent years due
to its revolutionary use in printing drugs tailored
to individual patient needs [1,2]. Selective laser
sintering (SLS) is an industrial 3D printing
technique which uses a powder bed to build up
the 3D object thanks to a laser which binds the
powder particles together. Advantages of SLS
technique include the fact that it is a solvent-free
process and offers relatively fast production.
Until today, a limited number of studies
investigating the production of drug dosage
forms using SLS have been reported [2,3].
2. MATERIALS AND METHODS
2.1. Materials
Carvedilol (CRV) was used as a model
substance in this study and it was donated by
Hemofarm (Vršac, Serbia). The following
excipients used to obtain 3D printing tablets:
polyvinyl alcohol (PVA, Merck), mannitol
(Parteck® M, Merck), Ludipress®
(coprocessed excipient consisting of 93%
lactose monohydrate, 3.5% crospovidone
(Kollidon® CL) and 3.5% povidone K30
(Kollidon® 30), BASF), talc (Merck) and
candurin (Candurin® Gold Sheen, Merck).
2.2. Preparation of formulations
The compositions of the formulations are
shown in Table 1.
Table 1. Composition of the formulations
Material Formulation 1 Formulation 2
CRV 10% 10%
PVA 55% 55%
Parteck® M 30% /
Ludipress® / 30%
Talc 2% 2%
Candurin®
Gold Sheen 3% 3%
Powder for 3D printing was obtained by mixing
all the components of the formulation and
sifting through a sieve with a diameter of 180
μm.
2.3. 3D printing of oral dosage forms
A cylindrical 3D models of the printed tablets
(8.00 mm diameter and 2.00 mm thickness)
were designed with Autodesk Fusion 360
software version 2.0.8809 (Autodesk Inc, San
Rafael, CA, USA), exported as a
stereolithography file (.stl) and printed with
Sintratec Kit 3D printer (Sintratec AG,
Switzerland). The printing parameters were
controlled using Sintratec 3D printer software.
After a series of variations in temperature and
laser speed, the optimal values of these
parameters used in the 3D printing process were
established and shown in Table 2.
Table 2. SLS 3D printing process parameters
Surface
Temperature
( ◦C)
Chamber
Temperature
( ◦C)
Laser
speed
(mm/s)
Hatch
space
80 ºC 70 ºC 60 250 μm
2.4. Mechanical properties of 3D tablets
Tablets (n = 10) were weighed on a Sartorius BP
210 D analytical balance (Sartorius, Goettingen,
Germany) and measured (diameter and
thickness) using a digital caliper (Vogel,
Kevelaer, Germany).
2.5. Powder X-ray diffraction analysis
(PXRD)
PXRD analysis was performed to assess
whether the laser induced amorphization of any
of the compounds, especially amorphization of
poorly soluble CRV. Samples were collected
using a Philips PW-1050 (Philips, The
Netherlands) diffractometer, operated at 40 kV
and 30 mA, using Ni-filtered Cu Kα radiation.
2.6. Dissolution and Drug Release Analysis
Dissolution testing was performed under nonsink
conditions using mini paddle apparatus
(Erweka DT 600, Germany) with a paddle
rotation speed of 50 rpm for 8 h, in 100 ml of
phosphate buffer (pH 6.8). The amount of
dissolved CRV was determined by HPLC
method using Dionex Ultimate 3000 (Thermo
Scientific, USA) HPLC system.
3. RESULTS AND DISCUSSION
3.1. 3D printing process
It was shown that SLS printer was able to
fabricate 3D tablets with CRV, as well as that
success of the printing process depended on the
used printing parameters.
3.2. Mechanical properties of 3D tablets
The dimensions of the obtained 3D tablets were
in accordance with the defined values of the
created 3D models (F1: 8.10 ± 0.08 mm
diameter and 2.10 ± 0.13 mm thickness, F2:
8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm
thickness). Significant variations in tablet
weight between formulations were not observed
(m1=0.146 ± 0.04; m2=0.136 ± 0.03).
3.3. Powder X-ray diffraction analysis
(PXRD)
Figure 1. The X-ray powder diffraction of F1
and F2.
3.4. Dissolution and Drug Release Analysis
Figure 2. Dissolution profiles of 3D printing
tablets
4. CONCLUSION
SLA represents a new chapter in 3D printing of
solid oral dosage forms and in individualized
therapy in particular. By adjusting the
formulation and process parameters, it was
possible to produce SLS tablets with coamorphous
CRV and PVA as a main polymer.
Complete drug release was achieved under non
sink conditions after 8 hours in phosphate
buffer. The tailoring of drug release might be
achieved by varying formulation factors as well
as process parameters, although it could be
governed by the composition of the whole
formulation.
PB  - Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo
C3  - 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
T1  - Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique
SP  - 210
EP  - 211
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4749
ER  - 

@conference{
author = "Pešić, Nikola and Krkobabić, Mirjana and Adamov, Ivana and Ibrić, Svetlana and Ivković, Branka and Medarević, Đorđe",
year = "2022",
abstract = "1. INTRODUCTION
When it comes to pharmacy, 3D printing has
gained immense popularity in recent years due
to its revolutionary use in printing drugs tailored
to individual patient needs [1,2]. Selective laser
sintering (SLS) is an industrial 3D printing
technique which uses a powder bed to build up
the 3D object thanks to a laser which binds the
powder particles together. Advantages of SLS
technique include the fact that it is a solvent-free
process and offers relatively fast production.
Until today, a limited number of studies
investigating the production of drug dosage
forms using SLS have been reported [2,3].
2. MATERIALS AND METHODS
2.1. Materials
Carvedilol (CRV) was used as a model
substance in this study and it was donated by
Hemofarm (Vršac, Serbia). The following
excipients used to obtain 3D printing tablets:
polyvinyl alcohol (PVA, Merck), mannitol
(Parteck® M, Merck), Ludipress®
(coprocessed excipient consisting of 93%
lactose monohydrate, 3.5% crospovidone
(Kollidon® CL) and 3.5% povidone K30
(Kollidon® 30), BASF), talc (Merck) and
candurin (Candurin® Gold Sheen, Merck).
2.2. Preparation of formulations
The compositions of the formulations are
shown in Table 1.
Table 1. Composition of the formulations
Material Formulation 1 Formulation 2
CRV 10% 10%
PVA 55% 55%
Parteck® M 30% /
Ludipress® / 30%
Talc 2% 2%
Candurin®
Gold Sheen 3% 3%
Powder for 3D printing was obtained by mixing
all the components of the formulation and
sifting through a sieve with a diameter of 180
μm.
2.3. 3D printing of oral dosage forms
A cylindrical 3D models of the printed tablets
(8.00 mm diameter and 2.00 mm thickness)
were designed with Autodesk Fusion 360
software version 2.0.8809 (Autodesk Inc, San
Rafael, CA, USA), exported as a
stereolithography file (.stl) and printed with
Sintratec Kit 3D printer (Sintratec AG,
Switzerland). The printing parameters were
controlled using Sintratec 3D printer software.
After a series of variations in temperature and
laser speed, the optimal values of these
parameters used in the 3D printing process were
established and shown in Table 2.
Table 2. SLS 3D printing process parameters
Surface
Temperature
( ◦C)
Chamber
Temperature
( ◦C)
Laser
speed
(mm/s)
Hatch
space
80 ºC 70 ºC 60 250 μm
2.4. Mechanical properties of 3D tablets
Tablets (n = 10) were weighed on a Sartorius BP
210 D analytical balance (Sartorius, Goettingen,
Germany) and measured (diameter and
thickness) using a digital caliper (Vogel,
Kevelaer, Germany).
2.5. Powder X-ray diffraction analysis
(PXRD)
PXRD analysis was performed to assess
whether the laser induced amorphization of any
of the compounds, especially amorphization of
poorly soluble CRV. Samples were collected
using a Philips PW-1050 (Philips, The
Netherlands) diffractometer, operated at 40 kV
and 30 mA, using Ni-filtered Cu Kα radiation.
2.6. Dissolution and Drug Release Analysis
Dissolution testing was performed under nonsink
conditions using mini paddle apparatus
(Erweka DT 600, Germany) with a paddle
rotation speed of 50 rpm for 8 h, in 100 ml of
phosphate buffer (pH 6.8). The amount of
dissolved CRV was determined by HPLC
method using Dionex Ultimate 3000 (Thermo
Scientific, USA) HPLC system.
3. RESULTS AND DISCUSSION
3.1. 3D printing process
It was shown that SLS printer was able to
fabricate 3D tablets with CRV, as well as that
success of the printing process depended on the
used printing parameters.
3.2. Mechanical properties of 3D tablets
The dimensions of the obtained 3D tablets were
in accordance with the defined values of the
created 3D models (F1: 8.10 ± 0.08 mm
diameter and 2.10 ± 0.13 mm thickness, F2:
8.13 ± 0.09 mm diameter and 2.10 ± 0.12 mm
thickness). Significant variations in tablet
weight between formulations were not observed
(m1=0.146 ± 0.04; m2=0.136 ± 0.03).
3.3. Powder X-ray diffraction analysis
(PXRD)
Figure 1. The X-ray powder diffraction of F1
and F2.
3.4. Dissolution and Drug Release Analysis
Figure 2. Dissolution profiles of 3D printing
tablets
4. CONCLUSION
SLA represents a new chapter in 3D printing of
solid oral dosage forms and in individualized
therapy in particular. By adjusting the
formulation and process parameters, it was
possible to produce SLS tablets with coamorphous
CRV and PVA as a main polymer.
Complete drug release was achieved under non
sink conditions after 8 hours in phosphate
buffer. The tailoring of drug release might be
achieved by varying formulation factors as well
as process parameters, although it could be
governed by the composition of the whole
formulation.",
publisher = "Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo",
journal = "9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts",
title = "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique",
pages = "210-211",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4749"
}

Pešić, N., Krkobabić, M., Adamov, I., Ibrić, S., Ivković, B.,& Medarević, Đ.. (2022). Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts
Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo., 210-211.
https://hdl.handle.net/21.15107/rcub_farfar_4749

Pešić N, Krkobabić M, Adamov I, Ibrić S, Ivković B, Medarević Đ. Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique. in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts. 2022;:210-211.
https://hdl.handle.net/21.15107/rcub_farfar_4749 .

Pešić, Nikola, Krkobabić, Mirjana, Adamov, Ivana, Ibrić, Svetlana, Ivković, Branka, Medarević, Đorđe, "Oral dosage forms with carvedilol fabricated by selective laser sintering (SLS) 3D printing technique" in 9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts (2022):210-211,
https://hdl.handle.net/21.15107/rcub_farfar_4749 .

TY  - JOUR
AU  - Vasiljević, Ivana
AU  - Turković, Erna
AU  - Piller, Michael
AU  - Mirković, Miljana
AU  - Zimmer, Andreas
AU  - Aleksić, Ivana
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4318
AB  - 3D printing in dosage forms fabrication is in the focus of researchers, however, the attempts in multiparticulate units (MPUs) preparation are scarce. The aim of this study was to fabricate different size MPUs by selective laser sintering (SLS), using different polymers, and investigate their processability based on the SeDeM Expert System approach. MPUs (1- or 2-mm size) were prepared with model drug (ibuprofen or caffeine), polymer (poly(ethylene)oxide (PEO), ethyl cellulose (EC) or methacrylic acid-ethyl acrylate copolymer (MA-EA)) and printing aid. Comprehensive sample characterization was performed and experimentally obtained parameters were mathematically transformed and evaluated using the SeDeM Expert System framework. The obtained samples exhibited irregular shape, despite the spherical printing object design. Polymer incorporated notably affected MPUs properties. The obtained samples exhibited low bulk density, good flowability-, as well as stability-related parameters, which indicated their suitability for filling into capsules or sachets. Low density values implied that compressibility enhancing excipients may be required for MPUs incorporation in tablets. Samples containing EC and MA-EA were found suitable for compression, due to high compacts tensile strength. The obtained results indicate that SeDeM Expert System may extended from powder compressibility evaluation tool to framework facilitating powders/multiparticulate units processing.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach
VL  - 629
DO  - 10.1016/j.ijpharm.2022.122337
ER  - 

@article{
author = "Vasiljević, Ivana and Turković, Erna and Piller, Michael and Mirković, Miljana and Zimmer, Andreas and Aleksić, Ivana and Ibrić, Svetlana and Parojčić, Jelena",
year = "2022",
abstract = "3D printing in dosage forms fabrication is in the focus of researchers, however, the attempts in multiparticulate units (MPUs) preparation are scarce. The aim of this study was to fabricate different size MPUs by selective laser sintering (SLS), using different polymers, and investigate their processability based on the SeDeM Expert System approach. MPUs (1- or 2-mm size) were prepared with model drug (ibuprofen or caffeine), polymer (poly(ethylene)oxide (PEO), ethyl cellulose (EC) or methacrylic acid-ethyl acrylate copolymer (MA-EA)) and printing aid. Comprehensive sample characterization was performed and experimentally obtained parameters were mathematically transformed and evaluated using the SeDeM Expert System framework. The obtained samples exhibited irregular shape, despite the spherical printing object design. Polymer incorporated notably affected MPUs properties. The obtained samples exhibited low bulk density, good flowability-, as well as stability-related parameters, which indicated their suitability for filling into capsules or sachets. Low density values implied that compressibility enhancing excipients may be required for MPUs incorporation in tablets. Samples containing EC and MA-EA were found suitable for compression, due to high compacts tensile strength. The obtained results indicate that SeDeM Expert System may extended from powder compressibility evaluation tool to framework facilitating powders/multiparticulate units processing.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach",
volume = "629",
doi = "10.1016/j.ijpharm.2022.122337"
}

Vasiljević, I., Turković, E., Piller, M., Mirković, M., Zimmer, A., Aleksić, I., Ibrić, S.,& Parojčić, J.. (2022). Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach. in International Journal of Pharmaceutics
Elsevier B.V.., 629.
https://doi.org/10.1016/j.ijpharm.2022.122337

Vasiljević I, Turković E, Piller M, Mirković M, Zimmer A, Aleksić I, Ibrić S, Parojčić J. Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach. in International Journal of Pharmaceutics. 2022;629.
doi:10.1016/j.ijpharm.2022.122337 .

Vasiljević, Ivana, Turković, Erna, Piller, Michael, Mirković, Miljana, Zimmer, Andreas, Aleksić, Ivana, Ibrić, Svetlana, Parojčić, Jelena, "Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach" in International Journal of Pharmaceutics, 629 (2022),
https://doi.org/10.1016/j.ijpharm.2022.122337 . .

TY  - CONF
AU  - Adamov, Ivana
AU  - Tenić, Milica
AU  - Pešić, Nikola
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4573
AB  - In recent years, introduction of modern technologies, such as 3D printing, has
opened a new chapter and caused a paradigm shift from manufacturing of large-scale to
small batches of medicines tailored accordingly to the specific needs of patients (1). The aim
of this study was to formulate and fabricate two-layered tablets using digital light processing
(DLP) technique, which utilizes light irradiation to create solid objects from photoreactive
liquid resin in a layer-by-layer manner. Hydrochlorothiazide (HHT, 5%,w/w) and warfarin
sodium (VRN, 5%,w/w) were selected as model drugs, commonly used together in the
treatment of cardiovascular diseases. 3D printing process was initiated with 0.10% of
photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene
glycol) 400, 1:1, with the addition of water (10%,w/w). 3D tablets, with each of the active
substances in a separate layer, 8.00 mm in diameter and 1.50 mm thick, as well as combined
two-layered tablets with HHT and VRN in individual layers, were successfully printed with
Wanhao D8 printer. Dissolution test results showed immediate, but incomplete release of
VRN (81.47 ± 1.47%, after 45 min) from individual layers, while the release of HHT was
prolonged and complete (98.17 ± 3.11%, after 8 h). Significantly slower and incomplete
release of VRN and HHT from combined tablets was observed. The absence of interactions
and the presence of a layered structure were confirmed. DLP technique has a potential to
provide fast fabrication of combined tablets, while further optimization of formulation
factors is necessary in order to achieve complete drug release.
AB  - Poslednjih godina, uvođenjem savremenih tehnologija, poput 3D štampe, otvorilo se
novo poglavlje u načinu proizvodnje lekova i uslovilo razvoj fundamentalnih promena, pri
čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama
lekova prilagođenih specifičnim potrebama pacijenata (1). Cilj ovog istraživanja bio je da se
formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP) koja
omogućava dobijanje objekata mehanizmom nanošenja materijala “sloj po sloj” iz tečne
fotopolimerizacione smole pod uticajem svetlosti. Hidrohlortiazid (HHT, 5%, m/m) i
varfarin-natrijum (VRN, 5%, m/m) odabrani su kao model lekovite supstance, koje se obično
primenjuju zajedno u lečenju kardiovaskularnih bolesti. Proces 3D štampanja sproveden je u
prisustvu 0,10% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen
glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. 3D tablete, sa svakom
od aktivnih supstanci u posebnom sloju, prečnika 8,00 mm i debljine 1,50 mm, kao i
kombinovane dvoslojne tablete sa HHT i VRN u pojedinačnim slojevima, uspešno su
odštampane u Wanhao D8 štampaču. Prilikom ispitivanja brzine rastvaranja lekovite
supstance iz pojedinačnih slojeva, došlo je do trenutnog (81,47 ± 1,47% nakon 45 min), ali
nepotpunog oslobađanja VRN, dok je HHT u potpunosti oslobođen, prateći kinetiku
produženog oslobađanja (98,17 ± 3,11%, nakon 8 h). Zapaženo je znatno sporije i nepotpuno
oslobađanje VRN i HHT iz kombinovanih dvoslojnih tableta, nakon 8 h. Potvrđeno je
odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika ima potencijal da obezbedi
brzu izradu kombinovanih tableta, pri čemu je neophodna dalja optimizacija formulacionih
faktora u cilju postizanja potpunog oslobađanja lekovite supstance.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets
T1  - Primena fotopolimerizacione tehnike 3D štampe lekova u izradi dvoslojnih tableta
VL  - 72
IS  - 4 suplement
SP  - S410
EP  - S411
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4573
ER  - 

@conference{
author = "Adamov, Ivana and Tenić, Milica and Pešić, Nikola and Medarević, Đorđe and Ivković, Branka and Ibrić, Svetlana",
year = "2022",
abstract = "In recent years, introduction of modern technologies, such as 3D printing, has
opened a new chapter and caused a paradigm shift from manufacturing of large-scale to
small batches of medicines tailored accordingly to the specific needs of patients (1). The aim
of this study was to formulate and fabricate two-layered tablets using digital light processing
(DLP) technique, which utilizes light irradiation to create solid objects from photoreactive
liquid resin in a layer-by-layer manner. Hydrochlorothiazide (HHT, 5%,w/w) and warfarin
sodium (VRN, 5%,w/w) were selected as model drugs, commonly used together in the
treatment of cardiovascular diseases. 3D printing process was initiated with 0.10% of
photoinitiator, at a constant ratio of poly(ethylene glycol)diacrylate and poly(ethylene
glycol) 400, 1:1, with the addition of water (10%,w/w). 3D tablets, with each of the active
substances in a separate layer, 8.00 mm in diameter and 1.50 mm thick, as well as combined
two-layered tablets with HHT and VRN in individual layers, were successfully printed with
Wanhao D8 printer. Dissolution test results showed immediate, but incomplete release of
VRN (81.47 ± 1.47%, after 45 min) from individual layers, while the release of HHT was
prolonged and complete (98.17 ± 3.11%, after 8 h). Significantly slower and incomplete
release of VRN and HHT from combined tablets was observed. The absence of interactions
and the presence of a layered structure were confirmed. DLP technique has a potential to
provide fast fabrication of combined tablets, while further optimization of formulation
factors is necessary in order to achieve complete drug release., Poslednjih godina, uvođenjem savremenih tehnologija, poput 3D štampe, otvorilo se
novo poglavlje u načinu proizvodnje lekova i uslovilo razvoj fundamentalnih promena, pri
čemu serijska proizvodnja velikih šarži pretenduje da bude zamenjena malim serijama
lekova prilagođenih specifičnim potrebama pacijenata (1). Cilj ovog istraživanja bio je da se
formulišu i izrade dvoslojne tablete primenom tehnike digitalne obrade svetlosti (DLP) koja
omogućava dobijanje objekata mehanizmom nanošenja materijala “sloj po sloj” iz tečne
fotopolimerizacione smole pod uticajem svetlosti. Hidrohlortiazid (HHT, 5%, m/m) i
varfarin-natrijum (VRN, 5%, m/m) odabrani su kao model lekovite supstance, koje se obično
primenjuju zajedno u lečenju kardiovaskularnih bolesti. Proces 3D štampanja sproveden je u
prisustvu 0,10% fotoinicijatora, pri konstantnom masenom odnosu poli(etilen
glikol)diakrilata i poli(etilen glikola) 400, 1:1, uz dodatak 10% vode. 3D tablete, sa svakom
od aktivnih supstanci u posebnom sloju, prečnika 8,00 mm i debljine 1,50 mm, kao i
kombinovane dvoslojne tablete sa HHT i VRN u pojedinačnim slojevima, uspešno su
odštampane u Wanhao D8 štampaču. Prilikom ispitivanja brzine rastvaranja lekovite
supstance iz pojedinačnih slojeva, došlo je do trenutnog (81,47 ± 1,47% nakon 45 min), ali
nepotpunog oslobađanja VRN, dok je HHT u potpunosti oslobođen, prateći kinetiku
produženog oslobađanja (98,17 ± 3,11%, nakon 8 h). Zapaženo je znatno sporije i nepotpuno
oslobađanje VRN i HHT iz kombinovanih dvoslojnih tableta, nakon 8 h. Potvrđeno je
odsustvo interakcija i prisustvo slojevite strukture. DLP tehnika ima potencijal da obezbedi
brzu izradu kombinovanih tableta, pri čemu je neophodna dalja optimizacija formulacionih
faktora u cilju postizanja potpunog oslobađanja lekovite supstance.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets, Primena fotopolimerizacione tehnike 3D štampe lekova u izradi dvoslojnih tableta",
volume = "72",
number = "4 suplement",
pages = "S410-S411",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4573"
}

Adamov, I., Tenić, M., Pešić, N., Medarević, Đ., Ivković, B.,& Ibrić, S.. (2022). Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S410-S411.
https://hdl.handle.net/21.15107/rcub_farfar_4573

Adamov I, Tenić M, Pešić N, Medarević Đ, Ivković B, Ibrić S. Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets. in Arhiv za farmaciju. 2022;72(4 suplement):S410-S411.
https://hdl.handle.net/21.15107/rcub_farfar_4573 .

Adamov, Ivana, Tenić, Milica, Pešić, Nikola, Medarević, Đorđe, Ivković, Branka, Ibrić, Svetlana, "Application of 3D printing photopolymerization technique in the fabrication of two-layered tablets" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S410-S411,
https://hdl.handle.net/21.15107/rcub_farfar_4573 .

TY  - CONF
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4453
AB  - The fourth industrial revolution brought with it the development and application of
advanced, digital technologies, in all segments of the pharmaceutical industry: from the
discovery of new active substances to post-marketing monitoring of the drug. New, virtual
technologies are: artificial intelligence, quantum computing, blockchain,
telecommunications, Internet of Things, augmented, virtual and mixed reality. Many research
and development centers in the pharmaceutical industry use artificial intelligence
technologies in the discovery of new active substances, in silico modeling of drug release and
absorption, optimization of drug formulation composition and production process and
simulation of clinical trials. Blockchain technology is beginning to be used in drug
distribution and makes it easier to reliably track pharmaceutical products at every step of
the supply chain. In this way, the possibility of distributing counterfeit medicines can be
reduced to a minimum. Virtual reality is used for drug discovery and design, enabling 3D
visualization of drug molecular structures. In R&D laboratories, it is used in the planning of
experiments; it can also be used in pharmaceutical education. In Mixed Reality, elements
from the real and virtual worlds coexist, allowing users to "enter" the combined world of real
and digital and move through it using state-of-the-art tools and sensors. There are a number
of challenges that need to be overcome in order to accelerate the use of new and
revolutionary virtual technologies, but the benefits of applying these technologies and the
opportunities they provide in the advancement of the pharmaceutical industry are
promising.
AB  - Četvrta industrijska revolucija je donela sa sobom razvoj i primenu naprednih,
digitalnih tehnologija, u svim segmentima razvoja i rada farmaceutske industrije: od otkrića
novih aktivnih supstanci do postmarkentinškog praćenja leka. Nove, virtuelne tehnologije su:
veštačka inteligencija, kvantno računarstvo, blockchain, telekomunikacije, internet stvari,
proširena, virtuelna i mešovita stvarnost. U mnogim centrima istraživanja i razvoja u
farmaceutskoj industriji se koriste tehnologije veštačke inteligencije u otkriću novih aktivnih
supstanci, za in silico modelovanje oslobađanja i resorpcije leka, optimizaciju sastava
formulacije leka i procesa proizvodnje i simulacije kliničkih ispitivanja. Blockchain
tehnologija počinje da se koristi u distribuciji lekova i olakšava pouzdano praćenje
farmaceutskih proizvoda na svakom koraku lanca snabdevanja. Na ovaj način se može
smanjiti na minimum mogućnost distribucije falsifikovanih lekova i obezbediti bezbednost
distributivnog lanca. Virtuelna stvarnost se primenjuje za otkrivanje i dizajn lekova,
omogućavajući 3D vizualizaciju molekularnih struktura lekova. U laboratorijama se
primenjuje u planiranju eksperimenata; može se koristiti i u okviru farmaceutskog
obrazovanja, za obuku studenata. U Mešovitoj stvarnosti, elementi iz stvarnog i virtuelnog
sveta koegzistiraju, omogućavajući korisnicima da “uđu” u kombinovani svet realnog i
digitalnog i da se kreću kroz njega koristeći najsavremenije alate i senzore. U farmaceutskoj
industriji, Microsoft HoloLens je korišćen kao primer mešovite stvarnosti, koja će se koristiti
u različitim oblastima: od sinteze i razvoja lekova, analitičkih procedura, proizvodnje,
inspekcije, pa do pakovanja i čuvanja lekova. Postoji niz izazova koje treba prevazići kako bi
se ubrzala upotreba novih i revolucionarnih virtuelnih tehnologija, ali su prednosti primene
ovih tehnologija i mogućnosti koje pružaju u napretku farmaceutske industrije velike.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Challenges of the Industry 4.0: digital technologies in pharmaceutical industry
T1  - Izazovi četvrte industrijske revolucije: primena digitalnih tehnologija u farmaceutskoj industriji
VL  - 72
IS  - 4 suplement
SP  - S77
EP  - S78
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4453
ER  - 

@conference{
author = "Ibrić, Svetlana",
year = "2022",
abstract = "The fourth industrial revolution brought with it the development and application of
advanced, digital technologies, in all segments of the pharmaceutical industry: from the
discovery of new active substances to post-marketing monitoring of the drug. New, virtual
technologies are: artificial intelligence, quantum computing, blockchain,
telecommunications, Internet of Things, augmented, virtual and mixed reality. Many research
and development centers in the pharmaceutical industry use artificial intelligence
technologies in the discovery of new active substances, in silico modeling of drug release and
absorption, optimization of drug formulation composition and production process and
simulation of clinical trials. Blockchain technology is beginning to be used in drug
distribution and makes it easier to reliably track pharmaceutical products at every step of
the supply chain. In this way, the possibility of distributing counterfeit medicines can be
reduced to a minimum. Virtual reality is used for drug discovery and design, enabling 3D
visualization of drug molecular structures. In R&D laboratories, it is used in the planning of
experiments; it can also be used in pharmaceutical education. In Mixed Reality, elements
from the real and virtual worlds coexist, allowing users to "enter" the combined world of real
and digital and move through it using state-of-the-art tools and sensors. There are a number
of challenges that need to be overcome in order to accelerate the use of new and
revolutionary virtual technologies, but the benefits of applying these technologies and the
opportunities they provide in the advancement of the pharmaceutical industry are
promising., Četvrta industrijska revolucija je donela sa sobom razvoj i primenu naprednih,
digitalnih tehnologija, u svim segmentima razvoja i rada farmaceutske industrije: od otkrića
novih aktivnih supstanci do postmarkentinškog praćenja leka. Nove, virtuelne tehnologije su:
veštačka inteligencija, kvantno računarstvo, blockchain, telekomunikacije, internet stvari,
proširena, virtuelna i mešovita stvarnost. U mnogim centrima istraživanja i razvoja u
farmaceutskoj industriji se koriste tehnologije veštačke inteligencije u otkriću novih aktivnih
supstanci, za in silico modelovanje oslobađanja i resorpcije leka, optimizaciju sastava
formulacije leka i procesa proizvodnje i simulacije kliničkih ispitivanja. Blockchain
tehnologija počinje da se koristi u distribuciji lekova i olakšava pouzdano praćenje
farmaceutskih proizvoda na svakom koraku lanca snabdevanja. Na ovaj način se može
smanjiti na minimum mogućnost distribucije falsifikovanih lekova i obezbediti bezbednost
distributivnog lanca. Virtuelna stvarnost se primenjuje za otkrivanje i dizajn lekova,
omogućavajući 3D vizualizaciju molekularnih struktura lekova. U laboratorijama se
primenjuje u planiranju eksperimenata; može se koristiti i u okviru farmaceutskog
obrazovanja, za obuku studenata. U Mešovitoj stvarnosti, elementi iz stvarnog i virtuelnog
sveta koegzistiraju, omogućavajući korisnicima da “uđu” u kombinovani svet realnog i
digitalnog i da se kreću kroz njega koristeći najsavremenije alate i senzore. U farmaceutskoj
industriji, Microsoft HoloLens je korišćen kao primer mešovite stvarnosti, koja će se koristiti
u različitim oblastima: od sinteze i razvoja lekova, analitičkih procedura, proizvodnje,
inspekcije, pa do pakovanja i čuvanja lekova. Postoji niz izazova koje treba prevazići kako bi
se ubrzala upotreba novih i revolucionarnih virtuelnih tehnologija, ali su prednosti primene
ovih tehnologija i mogućnosti koje pružaju u napretku farmaceutske industrije velike.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Challenges of the Industry 4.0: digital technologies in pharmaceutical industry, Izazovi četvrte industrijske revolucije: primena digitalnih tehnologija u farmaceutskoj industriji",
volume = "72",
number = "4 suplement",
pages = "S77-S78",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4453"
}

Ibrić, S.. (2022). Challenges of the Industry 4.0: digital technologies in pharmaceutical industry. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S77-S78.
https://hdl.handle.net/21.15107/rcub_farfar_4453

Ibrić S. Challenges of the Industry 4.0: digital technologies in pharmaceutical industry. in Arhiv za farmaciju. 2022;72(4 suplement):S77-S78.
https://hdl.handle.net/21.15107/rcub_farfar_4453 .

Ibrić, Svetlana, "Challenges of the Industry 4.0: digital technologies in pharmaceutical industry" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S77-S78,
https://hdl.handle.net/21.15107/rcub_farfar_4453 .

TY  - JOUR
AU  - Adamov, Ivana
AU  - Stanojević, Gordana
AU  - Medarević, Đorđe
AU  - Ivković, Branka
AU  - Kočović, David
AU  - Mirković, Dušica
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4275
AB  - The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.
PB  - Elsevier
T2  - International journal of pharmaceutics
T1  - Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique
VL  - 624
DO  - 10.1016/j.ijpharm.2022.122046
ER  - 

@article{
author = "Adamov, Ivana and Stanojević, Gordana and Medarević, Đorđe and Ivković, Branka and Kočović, David and Mirković, Dušica and Ibrić, Svetlana",
year = "2022",
abstract = "The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.",
publisher = "Elsevier",
journal = "International journal of pharmaceutics",
title = "Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique",
volume = "624",
doi = "10.1016/j.ijpharm.2022.122046"
}

Adamov, I., Stanojević, G., Medarević, Đ., Ivković, B., Kočović, D., Mirković, D.,& Ibrić, S.. (2022). Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique. in International journal of pharmaceutics
Elsevier., 624.
https://doi.org/10.1016/j.ijpharm.2022.122046

Adamov I, Stanojević G, Medarević Đ, Ivković B, Kočović D, Mirković D, Ibrić S. Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique. in International journal of pharmaceutics. 2022;624.
doi:10.1016/j.ijpharm.2022.122046 .

Adamov, Ivana, Stanojević, Gordana, Medarević, Đorđe, Ivković, Branka, Kočović, David, Mirković, Dušica, Ibrić, Svetlana, "Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique" in International journal of pharmaceutics, 624 (2022),
https://doi.org/10.1016/j.ijpharm.2022.122046 . .

TY  - JOUR
AU  - Ajdarić, Jovana
AU  - Ibrić, Svetlana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4068
AB  - The aim of this work was to apply the of Quality by Design concept in optimization of lyophilisation process in production of esomeprazole 40 mg powder for solution for injection/infusion. Optimization has been triggered by the product solution's sensitivity to oxygen, which leads to a fast decrease in pH value and limits allowable duration of air exposure. Lyophilizer capacity and number of ‘’good’’ vials of finished product are thereby significantly reduced, presenting serious obstacle for scale-up from 17,000 vials to 33,000 vials. With goal to maintain pH stable during production of an almost twice as big batch, a pre-freezing phase after filling, and before lyophilisation was introduced. Starting from the Quality Target Product Profile, Failure mode and effects analysis (FMEA) was applied for the purpose of defining Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), Critical Quality Attributes (CQAs) and control strategy for the production. It was confirmed that temperature of shelfs of −30 °C, as opposed to 20 °C, significantly extends the time for which esomeprazole solution remains stable. Finally, an artificial neural network model was built and trained in order to define the design space for the lyophilisation process. It was demonstrated that the pH of esomeprazole solution remains stable and in specification within the lyophilizer's shelf temperature range of −10 °C to −30 °C for 5–26 h.
PB  - Elsevier
T2  - Journal of Drug Delivery Science and Technology
T1  - Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept
VL  - 70
DO  - 10.1016/j.jddst.2022.103233
ER  - 

@article{
author = "Ajdarić, Jovana and Ibrić, Svetlana",
year = "2022",
abstract = "The aim of this work was to apply the of Quality by Design concept in optimization of lyophilisation process in production of esomeprazole 40 mg powder for solution for injection/infusion. Optimization has been triggered by the product solution's sensitivity to oxygen, which leads to a fast decrease in pH value and limits allowable duration of air exposure. Lyophilizer capacity and number of ‘’good’’ vials of finished product are thereby significantly reduced, presenting serious obstacle for scale-up from 17,000 vials to 33,000 vials. With goal to maintain pH stable during production of an almost twice as big batch, a pre-freezing phase after filling, and before lyophilisation was introduced. Starting from the Quality Target Product Profile, Failure mode and effects analysis (FMEA) was applied for the purpose of defining Critical Process Parameters (CPPs), Critical Material Attributes (CMAs), Critical Quality Attributes (CQAs) and control strategy for the production. It was confirmed that temperature of shelfs of −30 °C, as opposed to 20 °C, significantly extends the time for which esomeprazole solution remains stable. Finally, an artificial neural network model was built and trained in order to define the design space for the lyophilisation process. It was demonstrated that the pH of esomeprazole solution remains stable and in specification within the lyophilizer's shelf temperature range of −10 °C to −30 °C for 5–26 h.",
publisher = "Elsevier",
journal = "Journal of Drug Delivery Science and Technology",
title = "Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept",
volume = "70",
doi = "10.1016/j.jddst.2022.103233"
}

Ajdarić, J.,& Ibrić, S.. (2022). Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept. in Journal of Drug Delivery Science and Technology
Elsevier., 70.
https://doi.org/10.1016/j.jddst.2022.103233

Ajdarić J, Ibrić S. Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept. in Journal of Drug Delivery Science and Technology. 2022;70.
doi:10.1016/j.jddst.2022.103233 .

Ajdarić, Jovana, Ibrić, Svetlana, "Optimization of the lyophilisation process for esomeprazole 40 mg powder for solution for injection/infusion using quality by design concept" in Journal of Drug Delivery Science and Technology, 70 (2022),
https://doi.org/10.1016/j.jddst.2022.103233 . .

TY  - CONF
AU  - Ćirin-Varađan, Slobodanka
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
AU  - Aleksić, Ivana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4671
AB  - The lack of directly compressible excipients and the introduction of the high-speed
manufacturing machines have further increased the interest in the development of co-processed
excipients. In the present study, in situ fluidized bed melt granulation (FBMG) as an environmental
friendly and cost-effective method, was applied to co-process the most common filler, lactose
monohydrate, with lipid excipients glyceryl dibehenate (Compritol ® 888 ATO) or glyceryl
palmitostearate (Precirol ® ATO 5) known for their antiadhesive, lubricant and flowing aid properties
(1, 2). The goal of this study was to develop the lipid-based co-processed excipients and to investigate
their flowability and tableting properties using a solvent-free and eco-friendly, FBMG method.
The flow properties of the tested samples (the single-component excipients, their physical
mixtures, lactose (85% (w/w)) co-processed with Precirol® or Compritol ® (15% (w/w)), and
commercially available lactose-based co-processed excipients (Retalac ® and Ludipress®) were
evaluated by Carr index and Hausner ratio. Dynamic compaction analysis of the investigated excipients
was performed on a single punch instrumented tablet press (GTP D series, Gamlen Tableting Ltd, UK).
Comparable or even better flowability of co-processed excipients obtained via in situ FBMG, in
comparison to commercial co-processed excipients indicate their suitability for direct compression. Co-
processed excipients with Precirol ® and Compritol ®, as well as the corresponding physical mixtures,
showed two to almost three times lower values of total work of compression than those obtained for
commercial lactose-based excipients. Furthermore, co-processed excipients prepared with lipid
excipients showed up to 50-fold lower detachment work and up to 20-fold lower ejection work than
those obtained for Retalac ® and Ludipress®. Superior antiadhesive and lubricating properties of the
excipients prepared by in situ FBMG can be attributed to the properties of lipid excipients. Both
commercially available and the investigated co-processed excipients, prepared with lipid excipients,
showed relatively high tensile strength values (>1.7 MPa).
The results presented in this study indicate that in situ fluidized bed melt granulation can be
used as suitable co-processing technique, as a time and energy less consuming method in comparison
with commonly applied techniques such as spray drying and wet granulation. According to the results
obtained, by co-processing lactose with selected lipid excipients excellent flowability, as well as
improved tableting properties can be achieved. Novel co-processed excipients were even found to be
highly superior regarding their antiadhesive and lubricating properties in comparison to commercial
lactose-based co-processed excipients.
AB  - Nedostatak direktno kompresibilnih ekscipijenasa i uvođenje proizvodne opreme velike brzine
rada dodatno su povećali interesovanje za razvoj koprocesovanih ekscipijenasa. U ovoj studiji, in situ
granulacija topljenjem u uređaju tipa fluidizirajućeg sistema (eng. fluidized bed melt granulation,
FBMG), kao ekološki prihvatljiva i ekonomična metoda, primenjena je za koprocesovanje najčešće
korišćenog sredstva za dopunjavanje, laktoze, monohidrata, sa lipidnim ekscipijensima,
glicerildibehenatom (Compritol® 888 ATO) ili glicerilpalmitostearatom (Precirol® ATO 5), koji su
poznati po svojim antiadhezivnim, lubrikatnim i protočnim osobinama (1, 2). Cilj ovog ispitivanja je bio
razvoj novih koprocesovanih ekscipijenasa na bazi lipida primenom ekološki prihvatljive metode, koja
ne zahteva upotrebu rastvarača, i ispitivanje njihove protočnosti i tabletabilnosti.
Protočne karakteristike ispitivanih uzoraka (pojedinačni ekscipijensi, njihove fizičke smeše,
laktoza ((85% (m/m)) koprocesovana sa Precirol ®-om ili Compritol®-om (15% (m/m)), i komercijalno
dostupni koprocesovani ekscipijensi na bazi laktoze (Retalac ® i Ludipress® )) procenjene su na osnovu
vrednosti Carr-ovog indeksa i Hausner‐ovog odnosa. Laboratorijski simulator kompakcije (GTP D serija,
Gamlen Tableting Ltd, UK) korišćen je za dinamičku analizu kompakcije.
Uporedive ili čak bolje protočne karakteristike koprocesovanih ekscipijensa dobijenih metodom
in situ FBMG, u poređenju sa komercijalno dostupnim koprocesovanim ekscipijensima, ukazuju na
njihovu podobnost za direktnu kompresiju. Koprocesovani ekscipijensi sa Precirol®-om i Compritol ®-
om, kao i odgovarajuće fizičke smeše, pokazale su dva do skoro tri puta niže vrednosti ukupnog rada
kompresije od komercijalno dostupnih ekscipijenasa na bazi laktoze. Dodatno, koprocesovani
ekscipijensi na bazi lipida pokazali su do 50 puta manji rad odvajanja i do 20 puta manji rad izbacivanja
od Retalac ®-a i Ludipress® -a. Superiorna antiadhezivna i lubrikatna svojstva koprocesovanih
ekscipijenasa pripremljenih in situ FBMG mogu se pripisati lipidnim ekscipijensima. Komercijalno
dostupni kao i ispitivani koprocesovani ekscipijensi, na bazi lipidnih ekscipijenasa, pokazali su
relativno visoke vrednosti zatezne čvrstine (> 1,7 MPa).
Predstavljeni rezultati ukazuju na to da se granulacija topljenjem u uređaju tipa fluidizirajućeg
sistema može koristiti kao pogodna metoda za koprocesovanje, koja zahteva manji utrošak energije i
vremena u poređenju sa uobičajenim tehnikama, poput sušenja raspršivanjem ili vlažne granulacije.
Dobijeni rezultati pokazuju da se koprocesovanjem laktoze sa odabranim lipidnim ekscipijensima može
postići odlična protočnost, kao i poboljšana tabletabilnost. Novi koprocesovani ekscipijensi su čak
pokazali superiornije karakteristike u pogledu svojih antiadhezivnih i lubrikatnih karakteristika u
poređenju sa komercijalno dostupnim koprocesovanim ekscipijensima na bazi laktoze.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Application of solventless granulation method for developent of novel co‐processed excipeints
T1  - Primena metode granulacije bez upotrebe rastvarača u razvoju novih koprocesovanih ekscipijenasa
VL  - 71
IS  - 5 suplement
SP  - S80
EP  - S81
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4671
ER  - 

@conference{
author = "Ćirin-Varađan, Slobodanka and Đuriš, Jelena and Ibrić, Svetlana and Parojčić, Jelena and Aleksić, Ivana",
year = "2021",
abstract = "The lack of directly compressible excipients and the introduction of the high-speed
manufacturing machines have further increased the interest in the development of co-processed
excipients. In the present study, in situ fluidized bed melt granulation (FBMG) as an environmental
friendly and cost-effective method, was applied to co-process the most common filler, lactose
monohydrate, with lipid excipients glyceryl dibehenate (Compritol ® 888 ATO) or glyceryl
palmitostearate (Precirol ® ATO 5) known for their antiadhesive, lubricant and flowing aid properties
(1, 2). The goal of this study was to develop the lipid-based co-processed excipients and to investigate
their flowability and tableting properties using a solvent-free and eco-friendly, FBMG method.
The flow properties of the tested samples (the single-component excipients, their physical
mixtures, lactose (85% (w/w)) co-processed with Precirol® or Compritol ® (15% (w/w)), and
commercially available lactose-based co-processed excipients (Retalac ® and Ludipress®) were
evaluated by Carr index and Hausner ratio. Dynamic compaction analysis of the investigated excipients
was performed on a single punch instrumented tablet press (GTP D series, Gamlen Tableting Ltd, UK).
Comparable or even better flowability of co-processed excipients obtained via in situ FBMG, in
comparison to commercial co-processed excipients indicate their suitability for direct compression. Co-
processed excipients with Precirol ® and Compritol ®, as well as the corresponding physical mixtures,
showed two to almost three times lower values of total work of compression than those obtained for
commercial lactose-based excipients. Furthermore, co-processed excipients prepared with lipid
excipients showed up to 50-fold lower detachment work and up to 20-fold lower ejection work than
those obtained for Retalac ® and Ludipress®. Superior antiadhesive and lubricating properties of the
excipients prepared by in situ FBMG can be attributed to the properties of lipid excipients. Both
commercially available and the investigated co-processed excipients, prepared with lipid excipients,
showed relatively high tensile strength values (>1.7 MPa).
The results presented in this study indicate that in situ fluidized bed melt granulation can be
used as suitable co-processing technique, as a time and energy less consuming method in comparison
with commonly applied techniques such as spray drying and wet granulation. According to the results
obtained, by co-processing lactose with selected lipid excipients excellent flowability, as well as
improved tableting properties can be achieved. Novel co-processed excipients were even found to be
highly superior regarding their antiadhesive and lubricating properties in comparison to commercial
lactose-based co-processed excipients., Nedostatak direktno kompresibilnih ekscipijenasa i uvođenje proizvodne opreme velike brzine
rada dodatno su povećali interesovanje za razvoj koprocesovanih ekscipijenasa. U ovoj studiji, in situ
granulacija topljenjem u uređaju tipa fluidizirajućeg sistema (eng. fluidized bed melt granulation,
FBMG), kao ekološki prihvatljiva i ekonomična metoda, primenjena je za koprocesovanje najčešće
korišćenog sredstva za dopunjavanje, laktoze, monohidrata, sa lipidnim ekscipijensima,
glicerildibehenatom (Compritol® 888 ATO) ili glicerilpalmitostearatom (Precirol® ATO 5), koji su
poznati po svojim antiadhezivnim, lubrikatnim i protočnim osobinama (1, 2). Cilj ovog ispitivanja je bio
razvoj novih koprocesovanih ekscipijenasa na bazi lipida primenom ekološki prihvatljive metode, koja
ne zahteva upotrebu rastvarača, i ispitivanje njihove protočnosti i tabletabilnosti.
Protočne karakteristike ispitivanih uzoraka (pojedinačni ekscipijensi, njihove fizičke smeše,
laktoza ((85% (m/m)) koprocesovana sa Precirol ®-om ili Compritol®-om (15% (m/m)), i komercijalno
dostupni koprocesovani ekscipijensi na bazi laktoze (Retalac ® i Ludipress® )) procenjene su na osnovu
vrednosti Carr-ovog indeksa i Hausner‐ovog odnosa. Laboratorijski simulator kompakcije (GTP D serija,
Gamlen Tableting Ltd, UK) korišćen je za dinamičku analizu kompakcije.
Uporedive ili čak bolje protočne karakteristike koprocesovanih ekscipijensa dobijenih metodom
in situ FBMG, u poređenju sa komercijalno dostupnim koprocesovanim ekscipijensima, ukazuju na
njihovu podobnost za direktnu kompresiju. Koprocesovani ekscipijensi sa Precirol®-om i Compritol ®-
om, kao i odgovarajuće fizičke smeše, pokazale su dva do skoro tri puta niže vrednosti ukupnog rada
kompresije od komercijalno dostupnih ekscipijenasa na bazi laktoze. Dodatno, koprocesovani
ekscipijensi na bazi lipida pokazali su do 50 puta manji rad odvajanja i do 20 puta manji rad izbacivanja
od Retalac ®-a i Ludipress® -a. Superiorna antiadhezivna i lubrikatna svojstva koprocesovanih
ekscipijenasa pripremljenih in situ FBMG mogu se pripisati lipidnim ekscipijensima. Komercijalno
dostupni kao i ispitivani koprocesovani ekscipijensi, na bazi lipidnih ekscipijenasa, pokazali su
relativno visoke vrednosti zatezne čvrstine (> 1,7 MPa).
Predstavljeni rezultati ukazuju na to da se granulacija topljenjem u uređaju tipa fluidizirajućeg
sistema može koristiti kao pogodna metoda za koprocesovanje, koja zahteva manji utrošak energije i
vremena u poređenju sa uobičajenim tehnikama, poput sušenja raspršivanjem ili vlažne granulacije.
Dobijeni rezultati pokazuju da se koprocesovanjem laktoze sa odabranim lipidnim ekscipijensima može
postići odlična protočnost, kao i poboljšana tabletabilnost. Novi koprocesovani ekscipijensi su čak
pokazali superiornije karakteristike u pogledu svojih antiadhezivnih i lubrikatnih karakteristika u
poređenju sa komercijalno dostupnim koprocesovanim ekscipijensima na bazi laktoze.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Application of solventless granulation method for developent of novel co‐processed excipeints, Primena metode granulacije bez upotrebe rastvarača u razvoju novih koprocesovanih ekscipijenasa",
volume = "71",
number = "5 suplement",
pages = "S80-S81",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4671"
}

Ćirin-Varađan, S., Đuriš, J., Ibrić, S., Parojčić, J.,& Aleksić, I.. (2021). Application of solventless granulation method for developent of novel co‐processed excipeints. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 71(5 suplement), S80-S81.
https://hdl.handle.net/21.15107/rcub_farfar_4671

Ćirin-Varađan S, Đuriš J, Ibrić S, Parojčić J, Aleksić I. Application of solventless granulation method for developent of novel co‐processed excipeints. in Arhiv za farmaciju. 2021;71(5 suplement):S80-S81.
https://hdl.handle.net/21.15107/rcub_farfar_4671 .

Ćirin-Varađan, Slobodanka, Đuriš, Jelena, Ibrić, Svetlana, Parojčić, Jelena, Aleksić, Ivana, "Application of solventless granulation method for developent of novel co‐processed excipeints" in Arhiv za farmaciju, 71, no. 5 suplement (2021):S80-S81,
https://hdl.handle.net/21.15107/rcub_farfar_4671 .

TY  - CONF
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Đikić, Teodora
AU  - Cvijić, Sandra
AU  - Ignjatović, Jelisaveta
AU  - Ibrić, Svetlana
AU  - Baralić, Katarina
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4896
PB  - Hellenic Society of Medicinal Chemistry
C3  - 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium
T1  - Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4896
ER  - 

@conference{
author = "Đoković, Nemanja and Ružić, Dušan and Đikić, Teodora and Cvijić, Sandra and Ignjatović, Jelisaveta and Ibrić, Svetlana and Baralić, Katarina and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Nikolić, Katarina",
year = "2021",
publisher = "Hellenic Society of Medicinal Chemistry",
journal = "18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium",
title = "Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4896"
}

Đoković, N., Ružić, D., Đikić, T., Cvijić, S., Ignjatović, J., Ibrić, S., Baralić, K., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D.,& Nikolić, K.. (2021). Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach. in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium
Hellenic Society of Medicinal Chemistry..
https://hdl.handle.net/21.15107/rcub_farfar_4896

Đoković N, Ružić D, Đikić T, Cvijić S, Ignjatović J, Ibrić S, Baralić K, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Nikolić K. Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach. in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4896 .

Đoković, Nemanja, Ružić, Dušan, Đikić, Teodora, Cvijić, Sandra, Ignjatović, Jelisaveta, Ibrić, Svetlana, Baralić, Katarina, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Nikolić, Katarina, "Seeking SARS-CoV-2 Mpro inhibitors through an integrative in silico approach" in 18th Hellenic Symposium on Medicinal Chemistry, 25 - 27 February 2021, Online Symposium (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4896 .

TY  - JOUR
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Đikić, Teodora
AU  - Cvijić, Sandra
AU  - Ignjatović, Jelisaveta
AU  - Ibrić, Svetlana
AU  - Baralić, Katarina
AU  - Buha-Đorđević, Aleksandra
AU  - Ćurčić, Marijana
AU  - Đukić-Ćosić, Danijela
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3830
AB  - Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.
PB  - John Wiley and Sons Inc
T2  - Molecular Informatics
T1  - An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease
VL  - 40
IS  - 5
DO  - 10.1002/minf.202000187
ER  - 

@article{
author = "Đoković, Nemanja and Ružić, Dušan and Đikić, Teodora and Cvijić, Sandra and Ignjatović, Jelisaveta and Ibrić, Svetlana and Baralić, Katarina and Buha-Đorđević, Aleksandra and Ćurčić, Marijana and Đukić-Ćosić, Danijela and Nikolić, Katarina",
year = "2021",
abstract = "Considering the urgent need for novel therapeutics in ongoing COVID-19 pandemic, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we designed an integrative in silico drug repurposing approach for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro). To screen FDA-approved drugs, we implemented structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data mining analysis of drug-gene-COVID-19 association. Through presented approach, we selected the most promising FDA approved drugs for further COVID-19 drug development campaigns and analysed them in context of available experimental data. To the best of our knowledge, this is unique in silico study which integrates structure-based molecular modeling of Mpro inhibitors with predictions of their tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.",
publisher = "John Wiley and Sons Inc",
journal = "Molecular Informatics",
title = "An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease",
volume = "40",
number = "5",
doi = "10.1002/minf.202000187"
}

Đoković, N., Ružić, D., Đikić, T., Cvijić, S., Ignjatović, J., Ibrić, S., Baralić, K., Buha-Đorđević, A., Ćurčić, M., Đukić-Ćosić, D.,& Nikolić, K.. (2021). An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease. in Molecular Informatics
John Wiley and Sons Inc., 40(5).
https://doi.org/10.1002/minf.202000187

Đoković N, Ružić D, Đikić T, Cvijić S, Ignjatović J, Ibrić S, Baralić K, Buha-Đorđević A, Ćurčić M, Đukić-Ćosić D, Nikolić K. An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease. in Molecular Informatics. 2021;40(5).
doi:10.1002/minf.202000187 .

Đoković, Nemanja, Ružić, Dušan, Đikić, Teodora, Cvijić, Sandra, Ignjatović, Jelisaveta, Ibrić, Svetlana, Baralić, Katarina, Buha-Đorđević, Aleksandra, Ćurčić, Marijana, Đukić-Ćosić, Danijela, Nikolić, Katarina, "An Integrative in silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease" in Molecular Informatics, 40, no. 5 (2021),
https://doi.org/10.1002/minf.202000187 . .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Petrović, Miloš
AU  - Cvijić, Sandra
AU  - Tomić, Nataša
AU  - Stojanović, Dušica
AU  - Ibrić, Svetlana
AU  - Uskoković, Petar
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4016
AB  - Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties and drug release profiles of gelatin-based films. The Fourier-transform infrared spectroscopy showed that hydrogen bonding between gelatin and PVP formed during printing. In the other blend, neither the esterification of PVA nor gelatin occurred. Differential scanning calorimetry revealed the presence of partial helical structures. In line with these results, the mechanical properties and drug release profiles were different for each blend. Formulation with gelatin-PVP and PRH showed higher tensile strength, hardness, and adhesive strength but slower drug release than formulation with gelatin-PVA and PRH. The in silico population simulations indicated increased drug bioavailability and decreased inter-individual variations in the resulting pharmacokinetic profiles compared to immediate-release tablets. Moreover, the simulation results suggested that reduced PRH daily dosing can be achieved with prolonged-release buccal films, which improves patient compliance.
PB  - MDPI
T2  - Pharmaceutics
T1  - 3d printed buccal films for prolonged-release of propranolol hydrochloride: Development, characterization and bioavailability prediction
VL  - 13
IS  - 12
DO  - 10.3390/pharmaceutics13122143
ER  - 

@article{
author = "Jovanović, Marija and Petrović, Miloš and Cvijić, Sandra and Tomić, Nataša and Stojanović, Dušica and Ibrić, Svetlana and Uskoković, Petar",
year = "2021",
abstract = "Gelatin-polyvinylpyrrolidone (PVP) and gelatin-poly(vinyl alcohol) (PVA) mucoadhesive buccal films loaded with propranolol hydrochloride (PRH) were prepared by semi-solid extrusion 3D printing. The aim of this study was to evaluate the effects of the synthetic polymers PVP and PVA on thermal and mechanical properties and drug release profiles of gelatin-based films. The Fourier-transform infrared spectroscopy showed that hydrogen bonding between gelatin and PVP formed during printing. In the other blend, neither the esterification of PVA nor gelatin occurred. Differential scanning calorimetry revealed the presence of partial helical structures. In line with these results, the mechanical properties and drug release profiles were different for each blend. Formulation with gelatin-PVP and PRH showed higher tensile strength, hardness, and adhesive strength but slower drug release than formulation with gelatin-PVA and PRH. The in silico population simulations indicated increased drug bioavailability and decreased inter-individual variations in the resulting pharmacokinetic profiles compared to immediate-release tablets. Moreover, the simulation results suggested that reduced PRH daily dosing can be achieved with prolonged-release buccal films, which improves patient compliance.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "3d printed buccal films for prolonged-release of propranolol hydrochloride: Development, characterization and bioavailability prediction",
volume = "13",
number = "12",
doi = "10.3390/pharmaceutics13122143"
}

Jovanović, M., Petrović, M., Cvijić, S., Tomić, N., Stojanović, D., Ibrić, S.,& Uskoković, P.. (2021). 3d printed buccal films for prolonged-release of propranolol hydrochloride: Development, characterization and bioavailability prediction. in Pharmaceutics
MDPI., 13(12).
https://doi.org/10.3390/pharmaceutics13122143

Jovanović M, Petrović M, Cvijić S, Tomić N, Stojanović D, Ibrić S, Uskoković P. 3d printed buccal films for prolonged-release of propranolol hydrochloride: Development, characterization and bioavailability prediction. in Pharmaceutics. 2021;13(12).
doi:10.3390/pharmaceutics13122143 .

Jovanović, Marija, Petrović, Miloš, Cvijić, Sandra, Tomić, Nataša, Stojanović, Dušica, Ibrić, Svetlana, Uskoković, Petar, "3d printed buccal films for prolonged-release of propranolol hydrochloride: Development, characterization and bioavailability prediction" in Pharmaceutics, 13, no. 12 (2021),
https://doi.org/10.3390/pharmaceutics13122143 . .

TY  - JOUR
AU  - Jovanović, Marija
AU  - Tomić, Nataša
AU  - Cvijić, Sandra
AU  - Stojanović, Dušica
AU  - Ibrić, Svetlana
AU  - Uskoković, Petar
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3804
AB  - This study processes and characterizes propranolol hydrochloride/gelatin mucoadhesivebuccal films.  Two types of gelatin are used:  Gelatin from porcine skin, type A (GA), and gelatinfrom bovine skin (GB). The influence of gelatin type on mechanical, mucoadhesive, and biopharma-ceutical characteristics of buccal films is evaluated. Fourier-Transfer infrared spectroscopy (FTIR)and differential scanning calorimetry (DSC) analysis show that GA with propranolol hydrochloride(PRH) in the film (GAP) formed a physical mixture, whereas GB with PRH (GBP) form a compound-complex. Results of mechanical testing (tensile test, hardness) revealed that GAP films exhibit higherelastic modulus, tensile strength, and hardness.  A mucoahesion test shows that GBP has higheradhesion strength, while GAP shows higher work of adhesion. Bothin vitrorelease study and insilico simulation indicated that processed films can provide effective drug transport through thebuccal mucosa. In silico simulation shows improved bioavailability from buccal films, in comparisonto the immediate-release tablets—indicating that the therapeutic drug dose can be markedly reduced.
PB  - MDPI AG
T2  - Pharmaceutics
T1  - Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties
VL  - 13
IS  - 2
SP  - 1
EP  - 19
DO  - 10.3390/pharmaceutics13020273
ER  - 

@article{
author = "Jovanović, Marija and Tomić, Nataša and Cvijić, Sandra and Stojanović, Dušica and Ibrić, Svetlana and Uskoković, Petar",
year = "2021",
abstract = "This study processes and characterizes propranolol hydrochloride/gelatin mucoadhesivebuccal films.  Two types of gelatin are used:  Gelatin from porcine skin, type A (GA), and gelatinfrom bovine skin (GB). The influence of gelatin type on mechanical, mucoadhesive, and biopharma-ceutical characteristics of buccal films is evaluated. Fourier-Transfer infrared spectroscopy (FTIR)and differential scanning calorimetry (DSC) analysis show that GA with propranolol hydrochloride(PRH) in the film (GAP) formed a physical mixture, whereas GB with PRH (GBP) form a compound-complex. Results of mechanical testing (tensile test, hardness) revealed that GAP films exhibit higherelastic modulus, tensile strength, and hardness.  A mucoahesion test shows that GBP has higheradhesion strength, while GAP shows higher work of adhesion. Bothin vitrorelease study and insilico simulation indicated that processed films can provide effective drug transport through thebuccal mucosa. In silico simulation shows improved bioavailability from buccal films, in comparisonto the immediate-release tablets—indicating that the therapeutic drug dose can be markedly reduced.",
publisher = "MDPI AG",
journal = "Pharmaceutics",
title = "Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties",
volume = "13",
number = "2",
pages = "1-19",
doi = "10.3390/pharmaceutics13020273"
}

Jovanović, M., Tomić, N., Cvijić, S., Stojanović, D., Ibrić, S.,& Uskoković, P.. (2021). Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. in Pharmaceutics
MDPI AG., 13(2), 1-19.
https://doi.org/10.3390/pharmaceutics13020273

Jovanović M, Tomić N, Cvijić S, Stojanović D, Ibrić S, Uskoković P. Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties. in Pharmaceutics. 2021;13(2):1-19.
doi:10.3390/pharmaceutics13020273 .

Jovanović, Marija, Tomić, Nataša, Cvijić, Sandra, Stojanović, Dušica, Ibrić, Svetlana, Uskoković, Petar, "Mucoadhesive gelatin buccal films with propranolol hydrochloride: Evaluation of mechanical, mucoadhesive, and biopharmaceutical properties" in Pharmaceutics, 13, no. 2 (2021):1-19,
https://doi.org/10.3390/pharmaceutics13020273 . .

TY  - JOUR
AU  - Ignjatović, Jelisaveta
AU  - Šušteršič, Tijana
AU  - Bodić, Aleksandar
AU  - Cvijić, Sandra
AU  - Ðuriš, Jelena
AU  - Rossi, Alessandra
AU  - Dobričić, Vladimir
AU  - Ibrić, Svetlana
AU  - Filipović, Nenad
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3993
AB  - In vitro assessment of dry powders for inhalation (DPIs) aerodynamic performance is an inevitable test in DPI development. However, contemporary trends in drug development also implicate the use of in silico methods, e.g., computational fluid dynamics (CFD) coupled with discrete phase modeling (DPM). The aim of this study was to compare the designed CFD-DPM outcomes with the results of three in vitro methods for aerodynamic assessment of solid lipid microparticle DPIs. The model was able to simulate particle-to-wall sticking and estimate fractions of particles that stick or bounce off the inhaler’s wall; however, we observed notable differences between the in silico and in vitro results. The predicted emitted fractions (EFs) were comparable to the in vitro determined EFs, whereas the predicted fine particle fractions (FPFs) were generally lower than the corresponding in vitro values. In addition, CFD-DPM predicted higher mass median aerodynamic diameter (MMAD) in comparison to the in vitro values. The outcomes of different in vitro methods also diverged, implying that these methods are not interchangeable. Overall, our results support the utility of CFD-DPM in the DPI development, but highlight the need for additional improvements in these models to capture all the key processes influencing aerodynamic performance of specific DPIs.
PB  - MDPI
T2  - Pharmaceutics
T1  - Comparative assessment of in vitro and in silico methods for aerodynamic characterization of powders for inhalation
VL  - 13
IS  - 11
DO  - 10.3390/pharmaceutics13111831
ER  - 

@article{
author = "Ignjatović, Jelisaveta and Šušteršič, Tijana and Bodić, Aleksandar and Cvijić, Sandra and Ðuriš, Jelena and Rossi, Alessandra and Dobričić, Vladimir and Ibrić, Svetlana and Filipović, Nenad",
year = "2021",
abstract = "In vitro assessment of dry powders for inhalation (DPIs) aerodynamic performance is an inevitable test in DPI development. However, contemporary trends in drug development also implicate the use of in silico methods, e.g., computational fluid dynamics (CFD) coupled with discrete phase modeling (DPM). The aim of this study was to compare the designed CFD-DPM outcomes with the results of three in vitro methods for aerodynamic assessment of solid lipid microparticle DPIs. The model was able to simulate particle-to-wall sticking and estimate fractions of particles that stick or bounce off the inhaler’s wall; however, we observed notable differences between the in silico and in vitro results. The predicted emitted fractions (EFs) were comparable to the in vitro determined EFs, whereas the predicted fine particle fractions (FPFs) were generally lower than the corresponding in vitro values. In addition, CFD-DPM predicted higher mass median aerodynamic diameter (MMAD) in comparison to the in vitro values. The outcomes of different in vitro methods also diverged, implying that these methods are not interchangeable. Overall, our results support the utility of CFD-DPM in the DPI development, but highlight the need for additional improvements in these models to capture all the key processes influencing aerodynamic performance of specific DPIs.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Comparative assessment of in vitro and in silico methods for aerodynamic characterization of powders for inhalation",
volume = "13",
number = "11",
doi = "10.3390/pharmaceutics13111831"
}

Ignjatović, J., Šušteršič, T., Bodić, A., Cvijić, S., Ðuriš, J., Rossi, A., Dobričić, V., Ibrić, S.,& Filipović, N.. (2021). Comparative assessment of in vitro and in silico methods for aerodynamic characterization of powders for inhalation. in Pharmaceutics
MDPI., 13(11).
https://doi.org/10.3390/pharmaceutics13111831

Ignjatović J, Šušteršič T, Bodić A, Cvijić S, Ðuriš J, Rossi A, Dobričić V, Ibrić S, Filipović N. Comparative assessment of in vitro and in silico methods for aerodynamic characterization of powders for inhalation. in Pharmaceutics. 2021;13(11).
doi:10.3390/pharmaceutics13111831 .

Ignjatović, Jelisaveta, Šušteršič, Tijana, Bodić, Aleksandar, Cvijić, Sandra, Ðuriš, Jelena, Rossi, Alessandra, Dobričić, Vladimir, Ibrić, Svetlana, Filipović, Nenad, "Comparative assessment of in vitro and in silico methods for aerodynamic characterization of powders for inhalation" in Pharmaceutics, 13, no. 11 (2021),
https://doi.org/10.3390/pharmaceutics13111831 . .

TY  - JOUR
AU  - Cvijić, Sandra
AU  - Ignjatović, Jelisaveta
AU  - Parojčić, Jelena
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3959
AB  - Computer-based (in silico) modeling & simulation tools have been embraced in different
fields of pharmaceutics for a variety of applications. Among these, physiologically-based
pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful
tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly
evaluated over the past few years, as demonstrated by several reports from the pharmaceutical
industry, and a number of research and review papers on this subject. Also, the leading regulatory
authorities have recently issued guidance on the use of PBPK modeling in formulation design. In
silico PBPK models can comprise different dosing routes (oral, intraoral, parenteral, inhalation,
ocular, dermal etc.), although the majority of published examples refer to modeling of oral drugs
performance. In order to facilitate the use of PBPK modeling tools, a couple of companies have
launched commercially available software such as GastroPlus™, Simcyp™ PBPK Simulator and
PK-Sim®. This paper highlights various application fields of PBPK/PBBM modeling, along with
the basic principles, advantages and limitations of this approach, and provides relevant examples
to demonstrate the practical utility of modeling & simulation tools in different stages of
formulation development.
AB  - Računarski podržano (in silico) modelovanje se danas koristi u različitim oblastima farmaceutskih nauka, sa širokom paletom primene. Kao jedan od in silico alata, fiziološki zasnovano farmakokinetičko/biofarmaceutsko modelovanje (PBPK/PBBM) se pokazalo posebno korisnim u razvoju farmaceutskih preparata. Strategije zasnovane na PBPK/PBBM modelovanju se poslednjih godina sve više razmatraju, što se vidi iz izveštaja farmaceutskih kompanija i velikog broja publikovanih istraživačkih i revijalnih radova na ovu temu. Takođe, vodeće regulatorne agencije su nedavno izdale vodiče koji se odnose na primenu PBPK modelovanja u razvoju farmaceutskih preparata. In silico PBPK modelovanje je primenjivo za različite puteve primene leka (peroralni, (intra)oralni, parenteralni, inhalacioni, okularni, dermalni itd), mada se najveći broj primera iz literature odnosi na modelovanje bioperformansi peroralno primenjenih lekova. Kako bi olakšale primenu PBPK modelovanja, nekoliko kompanija je razvilo komercijalno dostupne programske pakete, kao što su GastroPlus™, Simcyp™ PBPK Simulator i PK-Sim®. U ovom radu su istaknute različite mogućnosti primene PBPK/PBBM modelovanja, uključujući osnovne principe, prednosti i ograničenja. Takođe, prikazani su odgovarajući primeri koji opisuju praktičnu primenu modelovanja i simulacija u različitim fazama razvoja leka.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development
T1  - Uloga fiziološki-zasnovanog farmakokinetičkog/biofarmaceutskog modelovanja u razvoju farmaceutskih preparata
VL  - 71
IS  - 4
SP  - 318
EP  - 335
DO  - 10.5937/arhfarm71-32479
ER  - 

@article{
author = "Cvijić, Sandra and Ignjatović, Jelisaveta and Parojčić, Jelena and Ibrić, Svetlana",
year = "2021",
abstract = "Computer-based (in silico) modeling & simulation tools have been embraced in different
fields of pharmaceutics for a variety of applications. Among these, physiologically-based
pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful
tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly
evaluated over the past few years, as demonstrated by several reports from the pharmaceutical
industry, and a number of research and review papers on this subject. Also, the leading regulatory
authorities have recently issued guidance on the use of PBPK modeling in formulation design. In
silico PBPK models can comprise different dosing routes (oral, intraoral, parenteral, inhalation,
ocular, dermal etc.), although the majority of published examples refer to modeling of oral drugs
performance. In order to facilitate the use of PBPK modeling tools, a couple of companies have
launched commercially available software such as GastroPlus™, Simcyp™ PBPK Simulator and
PK-Sim®. This paper highlights various application fields of PBPK/PBBM modeling, along with
the basic principles, advantages and limitations of this approach, and provides relevant examples
to demonstrate the practical utility of modeling & simulation tools in different stages of
formulation development., Računarski podržano (in silico) modelovanje se danas koristi u različitim oblastima farmaceutskih nauka, sa širokom paletom primene. Kao jedan od in silico alata, fiziološki zasnovano farmakokinetičko/biofarmaceutsko modelovanje (PBPK/PBBM) se pokazalo posebno korisnim u razvoju farmaceutskih preparata. Strategije zasnovane na PBPK/PBBM modelovanju se poslednjih godina sve više razmatraju, što se vidi iz izveštaja farmaceutskih kompanija i velikog broja publikovanih istraživačkih i revijalnih radova na ovu temu. Takođe, vodeće regulatorne agencije su nedavno izdale vodiče koji se odnose na primenu PBPK modelovanja u razvoju farmaceutskih preparata. In silico PBPK modelovanje je primenjivo za različite puteve primene leka (peroralni, (intra)oralni, parenteralni, inhalacioni, okularni, dermalni itd), mada se najveći broj primera iz literature odnosi na modelovanje bioperformansi peroralno primenjenih lekova. Kako bi olakšale primenu PBPK modelovanja, nekoliko kompanija je razvilo komercijalno dostupne programske pakete, kao što su GastroPlus™, Simcyp™ PBPK Simulator i PK-Sim®. U ovom radu su istaknute različite mogućnosti primene PBPK/PBBM modelovanja, uključujući osnovne principe, prednosti i ograničenja. Takođe, prikazani su odgovarajući primeri koji opisuju praktičnu primenu modelovanja i simulacija u različitim fazama razvoja leka.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development, Uloga fiziološki-zasnovanog farmakokinetičkog/biofarmaceutskog modelovanja u razvoju farmaceutskih preparata",
volume = "71",
number = "4",
pages = "318-335",
doi = "10.5937/arhfarm71-32479"
}

Cvijić, S., Ignjatović, J., Parojčić, J.,& Ibrić, S.. (2021). The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(4), 318-335.
https://doi.org/10.5937/arhfarm71-32479

Cvijić S, Ignjatović J, Parojčić J, Ibrić S. The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development. in Arhiv za farmaciju. 2021;71(4):318-335.
doi:10.5937/arhfarm71-32479 .

Cvijić, Sandra, Ignjatović, Jelisaveta, Parojčić, Jelena, Ibrić, Svetlana, "The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development" in Arhiv za farmaciju, 71, no. 4 (2021):318-335,
https://doi.org/10.5937/arhfarm71-32479 . .

TY  - JOUR
AU  - Ignjatović, Jelisaveta
AU  - Đuriš, Jelena
AU  - Cvijić, Sandra
AU  - Dobričić, Vladimir
AU  - Montepietra, Agnese
AU  - Lombardi, Chiara
AU  - Ibrić, Svetlana
AU  - Rossi, Alessandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3709
AB  - The aim of this study was to optimize the parameters of the complex melt-emulsification process coupled with the spray-drying, in order to maintain the balance between solid lipid microparticles (SLMs) powders aerodynamic performance and salbutamol sulfate release rate. Quality target product profile was identified and risk management and principal component analysis were used to guide formulation development. Obtained dry powders for inhalation (DPIs) were evaluated in terms of SLMs size distribution, morphology, true density, drug content, solid state characterization studies, in vitro aerosol performance and in vitro drug release. SLMs micrographs indicated spherical, porous particles. Selected powders showed satisfactory aerosol performance with a mean mass aerodynamic diameter of around 3 μm and acceptable fine particle fraction (FPF). Addition of trehalose positively affected SLMs aerodynamic properties. The results of in vitro dissolution testing indicated that salbutamol sulfate release from the tested SLMs formulations was modified, in comparison to the raw drug release. In conclusion, SLMs in a form of DPIs were successfully developed and numerous factors that affects SLMs properties were identified in this study. Further research is required for full understanding of each factor's influence on SLMs properties and optimization of DPIs with maximized FPFs.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery
VL  - 156
DO  - 10.1016/j.ejps.2020.105588
ER  - 

@article{
author = "Ignjatović, Jelisaveta and Đuriš, Jelena and Cvijić, Sandra and Dobričić, Vladimir and Montepietra, Agnese and Lombardi, Chiara and Ibrić, Svetlana and Rossi, Alessandra",
year = "2021",
abstract = "The aim of this study was to optimize the parameters of the complex melt-emulsification process coupled with the spray-drying, in order to maintain the balance between solid lipid microparticles (SLMs) powders aerodynamic performance and salbutamol sulfate release rate. Quality target product profile was identified and risk management and principal component analysis were used to guide formulation development. Obtained dry powders for inhalation (DPIs) were evaluated in terms of SLMs size distribution, morphology, true density, drug content, solid state characterization studies, in vitro aerosol performance and in vitro drug release. SLMs micrographs indicated spherical, porous particles. Selected powders showed satisfactory aerosol performance with a mean mass aerodynamic diameter of around 3 μm and acceptable fine particle fraction (FPF). Addition of trehalose positively affected SLMs aerodynamic properties. The results of in vitro dissolution testing indicated that salbutamol sulfate release from the tested SLMs formulations was modified, in comparison to the raw drug release. In conclusion, SLMs in a form of DPIs were successfully developed and numerous factors that affects SLMs properties were identified in this study. Further research is required for full understanding of each factor's influence on SLMs properties and optimization of DPIs with maximized FPFs.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery",
volume = "156",
doi = "10.1016/j.ejps.2020.105588"
}

Ignjatović, J., Đuriš, J., Cvijić, S., Dobričić, V., Montepietra, A., Lombardi, C., Ibrić, S.,& Rossi, A.. (2021). Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 156.
https://doi.org/10.1016/j.ejps.2020.105588

Ignjatović J, Đuriš J, Cvijić S, Dobričić V, Montepietra A, Lombardi C, Ibrić S, Rossi A. Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery. in European Journal of Pharmaceutical Sciences. 2021;156.
doi:10.1016/j.ejps.2020.105588 .

Ignjatović, Jelisaveta, Đuriš, Jelena, Cvijić, Sandra, Dobričić, Vladimir, Montepietra, Agnese, Lombardi, Chiara, Ibrić, Svetlana, Rossi, Alessandra, "Development of solid lipid microparticles by melt-emulsification/spray-drying processes as carriers for pulmonary drug delivery" in European Journal of Pharmaceutical Sciences, 156 (2021),
https://doi.org/10.1016/j.ejps.2020.105588 . .

TY  - JOUR
AU  - Đuranović, Marija
AU  - Madžarević, Marijana
AU  - Ivković, Branka
AU  - Ibrić, Svetlana
AU  - Cvijić, Sandra
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4088
AB  - Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment
VL  - 610
DO  - 10.1016/j.ijpharm.2021.121194
ER  - 

@article{
author = "Đuranović, Marija and Madžarević, Marijana and Ivković, Branka and Ibrić, Svetlana and Cvijić, Sandra",
year = "2021",
abstract = "Paracetamol-loaded tablets were printed by fused deposition modelling technique, using polyvinyl alcohol as a backbone polymer and Affinisol™ HPMC as a plasticizer in all formulations. Four different strategies were applied in order to accelerate the drug release from the tablets. First, different release enhancers were added: sodium starch glycolate, croscarmellose sodium, Kollidon CL and mannitol. Kollidon CL and mannitol showed the greatest influence on the drug dissolution rate. The second strategy included lowering the infill density, which did not make any significant changes in dissolution profiles, according to the calculated similarity factor. Then the best two release enhancers from the first strategy were combined (Kollidon CL and mannitol) and this proved to be the most effective in the drug release acceleration. The fourth strategy, increasing the percentage of the release enhancers in formulation, revealed the importance of their concentration limits. In summary, the drug release accelerated from 58% released after 5 h to reaching the plateau within 2 h. In silico physiologically-based biopharmaceutics modelling showed that formulations with mannitol and Kollidon CL, especially the formulation containing a combination of these release enhancers, can provide relatively fast drug release and extent of drug absorption that complies with an immediate release tablet.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment",
volume = "610",
doi = "10.1016/j.ijpharm.2021.121194"
}

Đuranović, M., Madžarević, M., Ivković, B., Ibrić, S.,& Cvijić, S.. (2021). The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment. in International Journal of Pharmaceutics
Elsevier B.V.., 610.
https://doi.org/10.1016/j.ijpharm.2021.121194

Đuranović M, Madžarević M, Ivković B, Ibrić S, Cvijić S. The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment. in International Journal of Pharmaceutics. 2021;610.
doi:10.1016/j.ijpharm.2021.121194 .

Đuranović, Marija, Madžarević, Marijana, Ivković, Branka, Ibrić, Svetlana, Cvijić, Sandra, "The evaluation of the effect of different superdisintegrants on the drug release from FDM 3D printed tablets through different applied strategies: In vitro-in silico assessment" in International Journal of Pharmaceutics, 610 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121194 . .