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  - CONF
AU  - Kurćubić, Ivana
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5065
AB  - Multivariate analysis methods are a set of statistical
techniques that allow multiple variables to be tested
simultaneously. This makes them ideal for studying
relationships in large complex datasets. Pharmaceutical
products and drug manufacturing processes are complex
systems by nature and can therefore, be described using
multifactorial relationships. One of the commonly used
methods of multivariate analysis is principal components
analysis (PCA), which in short, transforms a large set of
variables into a smaller set of new variables, which are
designated as principal components (PCs). Principal
component represents a linear combination of the original
variables (Ferreira et Tobyn, 2015; Esbensen et Geladi,
2009). This study aimed to investigate the variability and
the possibility of differentiation of the formulated buccal
tablet formulations using PCA.
PB  - Macedonian Pharmaceutical Association
PB  - Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy
C3  - Macedonian Pharmaceutical Bulletin
T1  - Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis
VL  - 69
IS  - Suppl 1
SP  - 129
EP  - 130
DO  - 10.33320/maced.pharm.bull.2023.69.03.063
ER  - 

@conference{
author = "Kurćubić, Ivana and Ibrić, Svetlana and Đuriš, Jelena",
year = "2023",
abstract = "Multivariate analysis methods are a set of statistical
techniques that allow multiple variables to be tested
simultaneously. This makes them ideal for studying
relationships in large complex datasets. Pharmaceutical
products and drug manufacturing processes are complex
systems by nature and can therefore, be described using
multifactorial relationships. One of the commonly used
methods of multivariate analysis is principal components
analysis (PCA), which in short, transforms a large set of
variables into a smaller set of new variables, which are
designated as principal components (PCs). Principal
component represents a linear combination of the original
variables (Ferreira et Tobyn, 2015; Esbensen et Geladi,
2009). This study aimed to investigate the variability and
the possibility of differentiation of the formulated buccal
tablet formulations using PCA.",
publisher = "Macedonian Pharmaceutical Association, Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy",
journal = "Macedonian Pharmaceutical Bulletin",
title = "Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis",
volume = "69",
number = "Suppl 1",
pages = "129-130",
doi = "10.33320/maced.pharm.bull.2023.69.03.063"
}

Kurćubić, I., Ibrić, S.,& Đuriš, J.. (2023). Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis. in Macedonian Pharmaceutical Bulletin
Macedonian Pharmaceutical Association., 69(Suppl 1), 129-130.
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.063

Kurćubić I, Ibrić S, Đuriš J. Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis. in Macedonian Pharmaceutical Bulletin. 2023;69(Suppl 1):129-130.
doi:10.33320/maced.pharm.bull.2023.69.03.063 .

Kurćubić, Ivana, Ibrić, Svetlana, Đuriš, Jelena, "Assessment of mucoadhesive buccal tablets with propranolol hydrochloride using principal component analysis" in Macedonian Pharmaceutical Bulletin, 69, no. Suppl 1 (2023):129-130,
https://doi.org/10.33320/maced.pharm.bull.2023.69.03.063 . .

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  - JOUR
AU  - Kurćubić, Ivana
AU  - Vajić, Una-Jovana
AU  - Cvijić, Sandra
AU  - Crevar-Sakač, Milkica
AU  - Bogavac-Stanojević, Nataša
AU  - Miloradović, Zoran
AU  - Mihajlović-Stanojević, Nevena
AU  - Ivanov, Milan
AU  - Karanović, Danijela
AU  - Jovović, Đurđica
AU  - Đuriš, Jelena
PY  - 2021
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3990
AB  - The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension
VL  - 610
DO  - 10.1016/j.ijpharm.2021.121266
ER  - 

@article{
author = "Kurćubić, Ivana and Vajić, Una-Jovana and Cvijić, Sandra and Crevar-Sakač, Milkica and Bogavac-Stanojević, Nataša and Miloradović, Zoran and Mihajlović-Stanojević, Nevena and Ivanov, Milan and Karanović, Danijela and Jovović, Đurđica and Đuriš, Jelena",
year = "2021, 2021",
abstract = "The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 μg⋅h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension",
volume = "610",
doi = "10.1016/j.ijpharm.2021.121266"
}

Kurćubić, I., Vajić, U., Cvijić, S., Crevar-Sakač, M., Bogavac-Stanojević, N., Miloradović, Z., Mihajlović-Stanojević, N., Ivanov, M., Karanović, D., Jovović, Đ.,& Đuriš, J.. (2021). Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics
Elsevier B.V.., 610.
https://doi.org/10.1016/j.ijpharm.2021.121266

Kurćubić I, Vajić U, Cvijić S, Crevar-Sakač M, Bogavac-Stanojević N, Miloradović Z, Mihajlović-Stanojević N, Ivanov M, Karanović D, Jovović Đ, Đuriš J. Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension. in International Journal of Pharmaceutics. 2021;610.
doi:10.1016/j.ijpharm.2021.121266 .

Kurćubić, Ivana, Vajić, Una-Jovana, Cvijić, Sandra, Crevar-Sakač, Milkica, Bogavac-Stanojević, Nataša, Miloradović, Zoran, Mihajlović-Stanojević, Nevena, Ivanov, Milan, Karanović, Danijela, Jovović, Đurđica, Đuriš, Jelena, "Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension" in International Journal of Pharmaceutics, 610 (2021),
https://doi.org/10.1016/j.ijpharm.2021.121266 . .

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Cvijić, Sandra
AU  - Lukić, Milica
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3878
AB  - The development of solid dosage forms that are both convenient for administration and allow precise drug dosing for pediatric patients is one of the great challenges in contemporary pharmaceutical technology. The presented study has utilized propranolol hydrochloride, as one of the most frequently prescribed drugs that require manipulation of the conventional dosage forms to be administered to children. Multiparticulate oral formulations, powder- and granule-filled capsules, as well as mini tablets, were prepared and characterized in terms of their mass and content uniformity and compared to conventional marketed tablets split into halves and quarters. The obtained results have demonstrated the superiority of the multiparticulate formulations, in terms of their average mass and drug content uniformity. It has also been demonstrated that, due to improved flowability, granule-filled capsules are more conveniently compounded and provide higher  content  uniformity  compared  to  powder-filled  capsules.  The  presented  compounding method could be easily employed in community pharmacy settings. Mini tablets with high and uniform  content  of  propranolol  hydrochloride  have  been  successfully  prepared,  thereby presenting a viable strategy for efficient drug dose adjustment.
AB  - Razvoj čvrstih farmaceutskih oblika lekova koji su prikladni za primenu kod pedijatrijske populacije pacijenata, ali koji istovremeno omogućavaju i precizno doziranje lekovite supstance, predstavlja jedan od vodećih izazova u farmaceutskoj tehnologiji. Prikazana studija koristi propranolol-hidrohlorid, kao jedan od najčešće primenjivanih lekova koji zahteva prilagođavanje farmaceutskih oblika za primenu kod dece. Višečestični farmaceutski oblici u vidu kapsula napunjenih praškom ili granulama, kao i mini tablete, su izrađene i ispitane u pogledu variranja mase i ujednačenosti sadržaja lekovite supstance. Dobijeni rezultati su upoređeni sa variranjem mase uzoraka koji se dobijaju deljenjem konvencionalnih registrovanih tableta na polovine i četvrtine. Dobijeni rezultati ukazuju na superiornost višečestičnih farmaceutskih oblika, zbog visokog stepena ujednačenosti mase i sadržaja lekovite supstance. Takođe je pokazano da se, zbog unapređene protočnosti, kapsule lakše pune granulama u odnosu na praškove, kao i da takvi farmaceutski oblici imaju veću ujednačenost mase i sadržaja lekovite supstance. Predstavljeni postupak izrade je jednostavan za izvođenje u uslovima apoteke. Mini tablete sa visokim udelom i ujednačenim sadržajem propranolol-hidrohlorida su uspešno izrađene, i predstavljaju značajnu strategiju koja može da omogući efikasno prilagođavanje doze lekovite supstance.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: propranolol case study
T1  - Višečestične formulacije lekova za oralnu primenu kao strategija za precizno doziranje kod pedijatrijskih pacijenata - studija slučaja propranolola
VL  - 71
IS  - 2
SP  - 141
EP  - 159
DO  - 10.5937/arhfarm71‐30717
ER  - 

@article{
author = "Kurćubić, Ivana and Cvijić, Sandra and Lukić, Milica and Ibrić, Svetlana and Đuriš, Jelena",
year = "2021",
abstract = "The development of solid dosage forms that are both convenient for administration and allow precise drug dosing for pediatric patients is one of the great challenges in contemporary pharmaceutical technology. The presented study has utilized propranolol hydrochloride, as one of the most frequently prescribed drugs that require manipulation of the conventional dosage forms to be administered to children. Multiparticulate oral formulations, powder- and granule-filled capsules, as well as mini tablets, were prepared and characterized in terms of their mass and content uniformity and compared to conventional marketed tablets split into halves and quarters. The obtained results have demonstrated the superiority of the multiparticulate formulations, in terms of their average mass and drug content uniformity. It has also been demonstrated that, due to improved flowability, granule-filled capsules are more conveniently compounded and provide higher  content  uniformity  compared  to  powder-filled  capsules.  The  presented  compounding method could be easily employed in community pharmacy settings. Mini tablets with high and uniform  content  of  propranolol  hydrochloride  have  been  successfully  prepared,  thereby presenting a viable strategy for efficient drug dose adjustment., Razvoj čvrstih farmaceutskih oblika lekova koji su prikladni za primenu kod pedijatrijske populacije pacijenata, ali koji istovremeno omogućavaju i precizno doziranje lekovite supstance, predstavlja jedan od vodećih izazova u farmaceutskoj tehnologiji. Prikazana studija koristi propranolol-hidrohlorid, kao jedan od najčešće primenjivanih lekova koji zahteva prilagođavanje farmaceutskih oblika za primenu kod dece. Višečestični farmaceutski oblici u vidu kapsula napunjenih praškom ili granulama, kao i mini tablete, su izrađene i ispitane u pogledu variranja mase i ujednačenosti sadržaja lekovite supstance. Dobijeni rezultati su upoređeni sa variranjem mase uzoraka koji se dobijaju deljenjem konvencionalnih registrovanih tableta na polovine i četvrtine. Dobijeni rezultati ukazuju na superiornost višečestičnih farmaceutskih oblika, zbog visokog stepena ujednačenosti mase i sadržaja lekovite supstance. Takođe je pokazano da se, zbog unapređene protočnosti, kapsule lakše pune granulama u odnosu na praškove, kao i da takvi farmaceutski oblici imaju veću ujednačenost mase i sadržaja lekovite supstance. Predstavljeni postupak izrade je jednostavan za izvođenje u uslovima apoteke. Mini tablete sa visokim udelom i ujednačenim sadržajem propranolol-hidrohlorida su uspešno izrađene, i predstavljaju značajnu strategiju koja može da omogući efikasno prilagođavanje doze lekovite supstance.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: propranolol case study, Višečestične formulacije lekova za oralnu primenu kao strategija za precizno doziranje kod pedijatrijskih pacijenata - studija slučaja propranolola",
volume = "71",
number = "2",
pages = "141-159",
doi = "10.5937/arhfarm71‐30717"
}

Kurćubić, I., Cvijić, S., Lukić, M., Ibrić, S.,& Đuriš, J.. (2021). Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: propranolol case study. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(2), 141-159.
https://doi.org/10.5937/arhfarm71‐30717

Kurćubić I, Cvijić S, Lukić M, Ibrić S, Đuriš J. Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: propranolol case study. in Arhiv za farmaciju. 2021;71(2):141-159.
doi:10.5937/arhfarm71‐30717 .

Kurćubić, Ivana, Cvijić, Sandra, Lukić, Milica, Ibrić, Svetlana, Đuriš, Jelena, "Multiparticulate oral formulations as a viable strategy for precise drug dosing in pediatrics: propranolol case study" in Arhiv za farmaciju, 71, no. 2 (2021):141-159,
https://doi.org/10.5937/arhfarm71‐30717 . .

TY  - JOUR
AU  - Mudrić, Jelena
AU  - Šavikin, Katarina
AU  - Ðekić, Ljiljana
AU  - Pavlović, Stefan
AU  - Kurćubić, Ivana
AU  - Ibrić, Svetlana
AU  - Ðuriš, Jelena
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4014
AB  - Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.
PB  - MDPI
T2  - Pharmaceutics
T1  - Development of lipid-based gastroretentive delivery system for gentian extract by double emulsion–melt dispersion technique
VL  - 13
IS  - 12
DO  - 10.3390/pharmaceutics13122095
ER  - 

@article{
author = "Mudrić, Jelena and Šavikin, Katarina and Ðekić, Ljiljana and Pavlović, Stefan and Kurćubić, Ivana and Ibrić, Svetlana and Ðuriš, Jelena",
year = "2021",
abstract = "Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Development of lipid-based gastroretentive delivery system for gentian extract by double emulsion–melt dispersion technique",
volume = "13",
number = "12",
doi = "10.3390/pharmaceutics13122095"
}

Mudrić, J., Šavikin, K., Ðekić, L., Pavlović, S., Kurćubić, I., Ibrić, S.,& Ðuriš, J.. (2021). Development of lipid-based gastroretentive delivery system for gentian extract by double emulsion–melt dispersion technique. in Pharmaceutics
MDPI., 13(12).
https://doi.org/10.3390/pharmaceutics13122095

Mudrić J, Šavikin K, Ðekić L, Pavlović S, Kurćubić I, Ibrić S, Ðuriš J. Development of lipid-based gastroretentive delivery system for gentian extract by double emulsion–melt dispersion technique. in Pharmaceutics. 2021;13(12).
doi:10.3390/pharmaceutics13122095 .

Mudrić, Jelena, Šavikin, Katarina, Ðekić, Ljiljana, Pavlović, Stefan, Kurćubić, Ivana, Ibrić, Svetlana, Ðuriš, Jelena, "Development of lipid-based gastroretentive delivery system for gentian extract by double emulsion–melt dispersion technique" in Pharmaceutics, 13, no. 12 (2021),
https://doi.org/10.3390/pharmaceutics13122095 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Kurćubić, Ivana
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3952
AB  - Machine learning algorithms, and artificial intelligence in general, have a wide range of
applications in the field of pharmaceutical technology. Starting from the formulation
development, through a great potential for integration within the Quality by design framework,
these data science tools provide a better understanding of the pharmaceutical formulations and
respective processing. Machine learning algorithms can be especially helpful with the analysis of
the large volume of data generated by the Process analytical technologies. This paper provides a
brief explanation of the artificial neural networks, as one of the most frequently used machine
learning algorithms. The process of the network training and testing is described and accompanied
with illustrative examples of machine learning tools applied in the context of pharmaceutical
formulation development and related technologies, as well as an overview of the future trends.
Recently published studies on more sophisticated methods, such as deep neural networks and light
gradient boosting machine algorithm, have been described. The interested reader is also referred
to several official documents (guidelines) that pave the way for a more structured representation
of the machine learning models in their prospective submissions to the regulatory bodies.
AB  - Algoritmi mašinskog učenja, kao i veštačka inteligencija u širem smislu, su veoma značajni i primenjuju se u razne svrhe u okviru farmaceutske tehnologije. Počevši od razvoja formulacija, preko izuzetnog potencijala za integraciju u koncept dizajna kvaliteta (engl. Quality by design), algoritmi mašinskog učenja omogućavaju bolje razumevanje uticaja kako formulacionih faktora tako i odgovarajućih procesnih parametara. Algoritmi mašinskog učenja mogu biti od naročitog značaja i za analizu velikog obima podataka koji se generišu korišćenjem procesnih analitičkih tehnologija. U ovom radu su ukratko predstavljene veštačke neuronske mreže, kao jedan od najčešće korišćenih algoritama mašinskog učenja. Prikazani su procesi treninga i testiranja mreža, kao i ilustrativni primeri algoritama primenjenih za različite potrebe razvoja i/ili optimizacije farmaceutskih formulacija i postupaka njihove izrade. Takođe, dat je i pregled budućih trendova u ovoj oblasti, kao i novijih studija o sofisticiranim metodama, poput dubokih neuronskih mreža, i light gradient boosting algoritma. Zainteresovani čitaoci se takođe upućuju na nekoliko zvaničnih dokumenata (vodiča), po uzoru na koje mogu da se očekuju i preporuke za strukturiranu prezentaciju modela mašinskog učenja koji će se podnositi regulatornim telima u okviru dokumentacije koja se priprema za potrebe registracije novih lekova.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Review of machine learning algorithms´ application in pharmaceutical technology
T1  - Pregled primene algoritama mašinskog učenja u farmaceutskoj tehnologiji
VL  - 71
IS  - 4
SP  - 302
EP  - 317
DO  - 10.5937/arhfarm71-32499
ER  - 

@article{
author = "Đuriš, Jelena and Kurćubić, Ivana and Ibrić, Svetlana",
year = "2021",
abstract = "Machine learning algorithms, and artificial intelligence in general, have a wide range of
applications in the field of pharmaceutical technology. Starting from the formulation
development, through a great potential for integration within the Quality by design framework,
these data science tools provide a better understanding of the pharmaceutical formulations and
respective processing. Machine learning algorithms can be especially helpful with the analysis of
the large volume of data generated by the Process analytical technologies. This paper provides a
brief explanation of the artificial neural networks, as one of the most frequently used machine
learning algorithms. The process of the network training and testing is described and accompanied
with illustrative examples of machine learning tools applied in the context of pharmaceutical
formulation development and related technologies, as well as an overview of the future trends.
Recently published studies on more sophisticated methods, such as deep neural networks and light
gradient boosting machine algorithm, have been described. The interested reader is also referred
to several official documents (guidelines) that pave the way for a more structured representation
of the machine learning models in their prospective submissions to the regulatory bodies., Algoritmi mašinskog učenja, kao i veštačka inteligencija u širem smislu, su veoma značajni i primenjuju se u razne svrhe u okviru farmaceutske tehnologije. Počevši od razvoja formulacija, preko izuzetnog potencijala za integraciju u koncept dizajna kvaliteta (engl. Quality by design), algoritmi mašinskog učenja omogućavaju bolje razumevanje uticaja kako formulacionih faktora tako i odgovarajućih procesnih parametara. Algoritmi mašinskog učenja mogu biti od naročitog značaja i za analizu velikog obima podataka koji se generišu korišćenjem procesnih analitičkih tehnologija. U ovom radu su ukratko predstavljene veštačke neuronske mreže, kao jedan od najčešće korišćenih algoritama mašinskog učenja. Prikazani su procesi treninga i testiranja mreža, kao i ilustrativni primeri algoritama primenjenih za različite potrebe razvoja i/ili optimizacije farmaceutskih formulacija i postupaka njihove izrade. Takođe, dat je i pregled budućih trendova u ovoj oblasti, kao i novijih studija o sofisticiranim metodama, poput dubokih neuronskih mreža, i light gradient boosting algoritma. Zainteresovani čitaoci se takođe upućuju na nekoliko zvaničnih dokumenata (vodiča), po uzoru na koje mogu da se očekuju i preporuke za strukturiranu prezentaciju modela mašinskog učenja koji će se podnositi regulatornim telima u okviru dokumentacije koja se priprema za potrebe registracije novih lekova.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Review of machine learning algorithms´ application in pharmaceutical technology, Pregled primene algoritama mašinskog učenja u farmaceutskoj tehnologiji",
volume = "71",
number = "4",
pages = "302-317",
doi = "10.5937/arhfarm71-32499"
}

Đuriš, J., Kurćubić, I.,& Ibrić, S.. (2021). Review of machine learning algorithms´ application in pharmaceutical technology. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(4), 302-317.
https://doi.org/10.5937/arhfarm71-32499

Đuriš J, Kurćubić I, Ibrić S. Review of machine learning algorithms´ application in pharmaceutical technology. in Arhiv za farmaciju. 2021;71(4):302-317.
doi:10.5937/arhfarm71-32499 .

Đuriš, Jelena, Kurćubić, Ivana, Ibrić, Svetlana, "Review of machine learning algorithms´ application in pharmaceutical technology" in Arhiv za farmaciju, 71, no. 4 (2021):302-317,
https://doi.org/10.5937/arhfarm71-32499 . .

TY  - JOUR
AU  - Kurćubić, Ivana
AU  - Cvijić, Sandra
AU  - Filipčev, Bojana
AU  - Ignjatović, Jelisaveta
AU  - Ignjatović, Svetlana
AU  - Đuriš, Jelena
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3570
PB  - Elsevier
T2  - Reactive and Functional Polymers
T1  - Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling
VL  - 151
DO  - 10.1016/j.reactfunctpolym.2020.104587
ER  - 

@article{
author = "Kurćubić, Ivana and Cvijić, Sandra and Filipčev, Bojana and Ignjatović, Jelisaveta and Ignjatović, Svetlana and Đuriš, Jelena",
year = "2020",
publisher = "Elsevier",
journal = "Reactive and Functional Polymers",
title = "Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling",
volume = "151",
doi = "10.1016/j.reactfunctpolym.2020.104587"
}

Kurćubić, I., Cvijić, S., Filipčev, B., Ignjatović, J., Ignjatović, S.,& Đuriš, J.. (2020). Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling. in Reactive and Functional Polymers
Elsevier., 151.
https://doi.org/10.1016/j.reactfunctpolym.2020.104587

Kurćubić I, Cvijić S, Filipčev B, Ignjatović J, Ignjatović S, Đuriš J. Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling. in Reactive and Functional Polymers. 2020;151.
doi:10.1016/j.reactfunctpolym.2020.104587 .

Kurćubić, Ivana, Cvijić, Sandra, Filipčev, Bojana, Ignjatović, Jelisaveta, Ignjatović, Svetlana, Đuriš, Jelena, "Development of propranolol hydrochloride bilayer mucoadhesive buccal tablets supported by in silico physiologically-based modeling" in Reactive and Functional Polymers, 151 (2020),
https://doi.org/10.1016/j.reactfunctpolym.2020.104587 . .