TY  - CONF
AU  - Mudrić, Jelena
AU  - Arsenijević, Jelena
AU  - Maksimović, Zoran
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5307
AB  - Rosmarinic acid is a dominant component in the extracts of
Satureja kitaibelii (Gopčević et al., 2019). It is reported that
rosmarinic acid has antioxidant, anti-inflammatory,
antibacterial, antiviral and antimutagenic activity (Petersen
et al., 2003). The aim of this study was to develop an
optimal model by using RSM (response surface
methodology) and ANN (artificial neural network)
approach which can describe the influence of ethanol
concentration, temperature and time on the extraction of
rosmarinic acid from aerial parts of S. kitaibelii.
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 11-14 May
T1  - Comparison of artificial neural networks and response surface methodology for efficient extraction of rosmarinic acid from Satureja kitaibelii
SP  - 1
EP  - 2
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5307
ER  - 

@conference{
author = "Mudrić, Jelena and Arsenijević, Jelena and Maksimović, Zoran and Ibrić, Svetlana and Đuriš, Jelena",
year = "2021",
abstract = "Rosmarinic acid is a dominant component in the extracts of
Satureja kitaibelii (Gopčević et al., 2019). It is reported that
rosmarinic acid has antioxidant, anti-inflammatory,
antibacterial, antiviral and antimutagenic activity (Petersen
et al., 2003). The aim of this study was to develop an
optimal model by using RSM (response surface
methodology) and ANN (artificial neural network)
approach which can describe the influence of ethanol
concentration, temperature and time on the extraction of
rosmarinic acid from aerial parts of S. kitaibelii.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 11-14 May",
title = "Comparison of artificial neural networks and response surface methodology for efficient extraction of rosmarinic acid from Satureja kitaibelii",
pages = "1-2",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5307"
}

Mudrić, J., Arsenijević, J., Maksimović, Z., Ibrić, S.,& Đuriš, J.. (2021). Comparison of artificial neural networks and response surface methodology for efficient extraction of rosmarinic acid from Satureja kitaibelii. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 11-14 May
International Association for Pharmaceutical Technology, Mainz, Germany., 1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5307

Mudrić J, Arsenijević J, Maksimović Z, Ibrić S, Đuriš J. Comparison of artificial neural networks and response surface methodology for efficient extraction of rosmarinic acid from Satureja kitaibelii. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 11-14 May. 2021;:1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5307 .

Mudrić, Jelena, Arsenijević, Jelena, Maksimović, Zoran, Ibrić, Svetlana, Đuriš, Jelena, "Comparison of artificial neural networks and response surface methodology for efficient extraction of rosmarinic acid from Satureja kitaibelii" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology 11-14 May (2021):1-2,
https://hdl.handle.net/21.15107/rcub_farfar_5307 .

TY  - CONF
AU  - Aleksić, Ivana
AU  - Vasiljević, Ivana
AU  - Glišić, Teodora
AU  - Cvijić, Sandra
AU  - Parojčić, Jelena
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5316
AB  - Liquisolid technology has gained an increased attention as a
promising approach for the improvement of bioavailability
of poorly water soluble drugs. Suitable excipients with high
surface area and porous structure are used to convert liquid
lipophilic drugs or drug solutions/suspensions to powder
suitable for filling into capsules or compression into tablets.
Spireas (1) proposed this approach and pointed out the
importance of selecting the appropriate excipients (carrier
and coating material) in optimum amounts in order to
achieve both good flowability and acceptable compaction
properties, as prerequisites for industrial application.
Compaction properties of liquisolid systems have been
recognized as particularly challenging. However, the
published results regarding compression behavior of
liquisolid systems are still very limited (2, 3).
In the present study mesoporous, amorphous silica
excipients (Syloid® XDP 3050 and XDP 3150), optimized
to be used as carriers in liquisolid systems, were used for
preparation of liquisolid compacts. The aim of this study
was to evaluate the influence of carrier to coating ratio and
liquid content on flowability and compaction behavior of
liquisolid systems prepared with these novel excipients.
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11th-14th May 2021, Vienna, Austria, Virtual meeting
T1  - Liquisolid systems with mesoporous silica based carriers: An investigation of flow and compaction properties
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5316
ER  - 

@conference{
author = "Aleksić, Ivana and Vasiljević, Ivana and Glišić, Teodora and Cvijić, Sandra and Parojčić, Jelena",
year = "2021",
abstract = "Liquisolid technology has gained an increased attention as a
promising approach for the improvement of bioavailability
of poorly water soluble drugs. Suitable excipients with high
surface area and porous structure are used to convert liquid
lipophilic drugs or drug solutions/suspensions to powder
suitable for filling into capsules or compression into tablets.
Spireas (1) proposed this approach and pointed out the
importance of selecting the appropriate excipients (carrier
and coating material) in optimum amounts in order to
achieve both good flowability and acceptable compaction
properties, as prerequisites for industrial application.
Compaction properties of liquisolid systems have been
recognized as particularly challenging. However, the
published results regarding compression behavior of
liquisolid systems are still very limited (2, 3).
In the present study mesoporous, amorphous silica
excipients (Syloid® XDP 3050 and XDP 3150), optimized
to be used as carriers in liquisolid systems, were used for
preparation of liquisolid compacts. The aim of this study
was to evaluate the influence of carrier to coating ratio and
liquid content on flowability and compaction behavior of
liquisolid systems prepared with these novel excipients.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11th-14th May 2021, Vienna, Austria, Virtual meeting",
title = "Liquisolid systems with mesoporous silica based carriers: An investigation of flow and compaction properties",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5316"
}

Aleksić, I., Vasiljević, I., Glišić, T., Cvijić, S.,& Parojčić, J.. (2021). Liquisolid systems with mesoporous silica based carriers: An investigation of flow and compaction properties. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11th-14th May 2021, Vienna, Austria, Virtual meeting
International Association for Pharmaceutical Technology, Mainz, Germany..
https://hdl.handle.net/21.15107/rcub_farfar_5316

Aleksić I, Vasiljević I, Glišić T, Cvijić S, Parojčić J. Liquisolid systems with mesoporous silica based carriers: An investigation of flow and compaction properties. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11th-14th May 2021, Vienna, Austria, Virtual meeting. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_5316 .

Aleksić, Ivana, Vasiljević, Ivana, Glišić, Teodora, Cvijić, Sandra, Parojčić, Jelena, "Liquisolid systems with mesoporous silica based carriers: An investigation of flow and compaction properties" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11th-14th May 2021, Vienna, Austria, Virtual meeting (2021),
https://hdl.handle.net/21.15107/rcub_farfar_5316 .

TY  - CONF
AU  - Medarević, Đorđe
AU  - Dobričić, Vladimir
AU  - Krkobabić, Mirjana
AU  - Pešić, Nikola
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5326
AB  - INTRODUCTION
Formulation of solid dispersions (SDs) with water soluble polymers is one of the most efficient approaches for improving the dissolution rate of poorly soluble drugs. However, this formulation approach might not always be effective in improving the dissolution rate of drugs, especially those with pH-dependent solubility (1). The addition of alkalizers or acidifiers can solve this problem by changing pH in the near vicinity of drug particle surface, (microenvironmental pH) to the range where drug easily dissolves (2). This study evaluated the potential of several alkalizers for improving the dissolution rate of weakly acidic drug valsartan (VAL) from SDs prepared with hydrophilic polymers.
EXPERIMENTAL METHODS
Materials
VAL (Hemofarm a.d., Serbia) was used as a model poorly soluble drug. Hypromellose (HPMC E5, MethocelTM E5 LV premium, Dow Chemicals, USA) and polyvinylpyrrolidone (PVPK25, Kollidon® 25, BASF, Germany) were used as hydrophilic polymers for SDs preparation. Calcium oxide (CaO), magnesium oxide (MgO), sodium carbonate (Na2CO3) and meglumine (MEG) were used as alkalizers in solid dispersions.
SDs preparation
SDs were prepared in VAL:polymer:alkalizer (V:P:A) weight ratios 1:2:0.5, 1:2:1 and 1:2:2 (Table 1.). Additionally, binary SDs were prepared with VAL and polymer, but without alkalizer. VAL and polymer were dissolved in absolute ethanol on a magnetic stirred followed by dispersion of alkalizer. Ethanol was evaporated from dispersion using rotary evaporator (Büchi Rotavapor®, Büchi Labortechnik AG, Switzerland) at 50 °C. After further vacuum drying, mass was pulverized and sieved through sieve 355 μm.
SDs characterization
FT-IR spectroscopy (Nicolet iS10, Thermo Scientific, USA) was used to detect the presence of intermolecular interactions between drug, polymer and alkalizer. In vitro drug dissolution testing was performed using a rotating paddle apparatus in 900 ml of 0.1 M HCl as a dissolution medium, due to poor solubility of VAL in this medium. Microenvironmental pH (pHM) was estimated by measuring of pH of concentrated suspension of SD as an indicator of pH near the surface of drug particles.
RESULTS AND DISCUSSION
Slow and incomplete dissolution of VAL was observed from binary SDs with either PVP or HPMC. The addition of alkalizer resulted in a significantly improved VAL dissolution rate from SDs with both polymers, with faster VAL release from SDs with PVP. Na2CO3 showed the best performance in improving VAL dissolution rate amongst all tested alkalizers. Desired immediate release of VAL (>80% of VAL dissolved after 30 min) was achieved only from formulations SD8 and SD12 prepared with Na2CO3 in 1:2:1 and 1:2:2 V:P:A ratios, and also from formulation SD6 prepared with CaO in 1:2:1 V:P:A ratio). The addition of all alkalizers resulted in higher pHM (Table 1), independently of polymer used, but with considerable differences amongst tested alkalizers. The highest efficiency of Na2CO3 in improving VAL dissolution rate was not correlated with measured pHM, as higher pHM was measured for samples with CaO and MgO. However, the lowest pHM measured for samples with MEG was in accordance with the lowest capacity of this alkalizer to improve VAL dissolution rate. Due to the fastest VAL release achieved, SDs with PVP K25 and CaO or Na2CO3 were further characterized by FT-IR spectroscopy to detect the presence of intermolecular interactions in comparison with binary VAL:PVP SD (SDP) and corresponding physical mixtures (PMs). Shifting and decrease in intensity of VAL absorption band at 1729 cm-1 (carboxyl C=O stretching) and disappearance of peak at 1599 cm-1 (amide C=O stretching) was observed on the spectra of binary VAL:PVP SD compared to PM of equivalent composition, indicating that both C=O groups of VAL can be involved in intermolecular interaction with PVP. The same region of FT-IR spectra was changed in the case of SDs with alkalizer, where peak at 1729 cm-1 disappeared, while peak at 1599 cm-1 was reduced in intensity. Therefore, the same kind of interactions was observed for both binary and ternary SDs, which cannot explain observed faster VAL dissolution rate from ternary SDs with alkalizer.
CONCLUSION
The addition of alkalizer resulted in significantly improved VAL dissolution rate from SDs prepared with HPMC and PVP, wherein Na2CO3 showed the best performance amongst all tested alkalizers. Since slightly higher pHM was achieved with CaO and MgO, higher efficiency of Na2CO3 can be ascribed to its higher solubility which enables generation of pores in SDs, while release of carbon dioxide facilitates dispersion of particles in the dissolution medium and reduces their tendency towards aggregation.
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
T1  - Microenvironmental pH-modified solid dispersions for improving dissolution rate of valsartan
SP  - 1
EP  - 2
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5326
ER  - 

@conference{
author = "Medarević, Đorđe and Dobričić, Vladimir and Krkobabić, Mirjana and Pešić, Nikola and Ibrić, Svetlana",
year = "2021",
abstract = "INTRODUCTION
Formulation of solid dispersions (SDs) with water soluble polymers is one of the most efficient approaches for improving the dissolution rate of poorly soluble drugs. However, this formulation approach might not always be effective in improving the dissolution rate of drugs, especially those with pH-dependent solubility (1). The addition of alkalizers or acidifiers can solve this problem by changing pH in the near vicinity of drug particle surface, (microenvironmental pH) to the range where drug easily dissolves (2). This study evaluated the potential of several alkalizers for improving the dissolution rate of weakly acidic drug valsartan (VAL) from SDs prepared with hydrophilic polymers.
EXPERIMENTAL METHODS
Materials
VAL (Hemofarm a.d., Serbia) was used as a model poorly soluble drug. Hypromellose (HPMC E5, MethocelTM E5 LV premium, Dow Chemicals, USA) and polyvinylpyrrolidone (PVPK25, Kollidon® 25, BASF, Germany) were used as hydrophilic polymers for SDs preparation. Calcium oxide (CaO), magnesium oxide (MgO), sodium carbonate (Na2CO3) and meglumine (MEG) were used as alkalizers in solid dispersions.
SDs preparation
SDs were prepared in VAL:polymer:alkalizer (V:P:A) weight ratios 1:2:0.5, 1:2:1 and 1:2:2 (Table 1.). Additionally, binary SDs were prepared with VAL and polymer, but without alkalizer. VAL and polymer were dissolved in absolute ethanol on a magnetic stirred followed by dispersion of alkalizer. Ethanol was evaporated from dispersion using rotary evaporator (Büchi Rotavapor®, Büchi Labortechnik AG, Switzerland) at 50 °C. After further vacuum drying, mass was pulverized and sieved through sieve 355 μm.
SDs characterization
FT-IR spectroscopy (Nicolet iS10, Thermo Scientific, USA) was used to detect the presence of intermolecular interactions between drug, polymer and alkalizer. In vitro drug dissolution testing was performed using a rotating paddle apparatus in 900 ml of 0.1 M HCl as a dissolution medium, due to poor solubility of VAL in this medium. Microenvironmental pH (pHM) was estimated by measuring of pH of concentrated suspension of SD as an indicator of pH near the surface of drug particles.
RESULTS AND DISCUSSION
Slow and incomplete dissolution of VAL was observed from binary SDs with either PVP or HPMC. The addition of alkalizer resulted in a significantly improved VAL dissolution rate from SDs with both polymers, with faster VAL release from SDs with PVP. Na2CO3 showed the best performance in improving VAL dissolution rate amongst all tested alkalizers. Desired immediate release of VAL (>80% of VAL dissolved after 30 min) was achieved only from formulations SD8 and SD12 prepared with Na2CO3 in 1:2:1 and 1:2:2 V:P:A ratios, and also from formulation SD6 prepared with CaO in 1:2:1 V:P:A ratio). The addition of all alkalizers resulted in higher pHM (Table 1), independently of polymer used, but with considerable differences amongst tested alkalizers. The highest efficiency of Na2CO3 in improving VAL dissolution rate was not correlated with measured pHM, as higher pHM was measured for samples with CaO and MgO. However, the lowest pHM measured for samples with MEG was in accordance with the lowest capacity of this alkalizer to improve VAL dissolution rate. Due to the fastest VAL release achieved, SDs with PVP K25 and CaO or Na2CO3 were further characterized by FT-IR spectroscopy to detect the presence of intermolecular interactions in comparison with binary VAL:PVP SD (SDP) and corresponding physical mixtures (PMs). Shifting and decrease in intensity of VAL absorption band at 1729 cm-1 (carboxyl C=O stretching) and disappearance of peak at 1599 cm-1 (amide C=O stretching) was observed on the spectra of binary VAL:PVP SD compared to PM of equivalent composition, indicating that both C=O groups of VAL can be involved in intermolecular interaction with PVP. The same region of FT-IR spectra was changed in the case of SDs with alkalizer, where peak at 1729 cm-1 disappeared, while peak at 1599 cm-1 was reduced in intensity. Therefore, the same kind of interactions was observed for both binary and ternary SDs, which cannot explain observed faster VAL dissolution rate from ternary SDs with alkalizer.
CONCLUSION
The addition of alkalizer resulted in significantly improved VAL dissolution rate from SDs prepared with HPMC and PVP, wherein Na2CO3 showed the best performance amongst all tested alkalizers. Since slightly higher pHM was achieved with CaO and MgO, higher efficiency of Na2CO3 can be ascribed to its higher solubility which enables generation of pores in SDs, while release of carbon dioxide facilitates dispersion of particles in the dissolution medium and reduces their tendency towards aggregation.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting",
title = "Microenvironmental pH-modified solid dispersions for improving dissolution rate of valsartan",
pages = "1-2",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5326"
}

Medarević, Đ., Dobričić, V., Krkobabić, M., Pešić, N.,& Ibrić, S.. (2021). Microenvironmental pH-modified solid dispersions for improving dissolution rate of valsartan. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
International Association for Pharmaceutical Technology, Mainz, Germany., 1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5326

Medarević Đ, Dobričić V, Krkobabić M, Pešić N, Ibrić S. Microenvironmental pH-modified solid dispersions for improving dissolution rate of valsartan. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting. 2021;:1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5326 .

Medarević, Đorđe, Dobričić, Vladimir, Krkobabić, Mirjana, Pešić, Nikola, Ibrić, Svetlana, "Microenvironmental pH-modified solid dispersions for improving dissolution rate of valsartan" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting (2021):1-2,
https://hdl.handle.net/21.15107/rcub_farfar_5326 .

TY  - CONF
AU  - Krkobabić, Mirjana
AU  - Pešić, Nikola
AU  - Boljević, Gordana
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5325
AB  - INTRODUCTION
Application of the 3D printing in pharmacy make possible production of small batches of solid dosage forms for oral administration (printlets) with different dose and release characteristics that can be customized to specific patient needs [1]. Digital light processing (DLP), one type of 3D printing technology, is based on a UV-triggered localized photopolymerization process of liquid resins [2]. The aim of this study was 3D printing from photoreactive dispersions with different amounts of solid phase and characterization of obtained printlets.
MATERIALS
Different photoreactive dispersions were prepared from poly(ethylene glycol) diacrylate 700 (PEGDA 700, Sigma-Aldrich, Japan), poly(ethylene glycol) 400 (PEG 400, Fagron, Netherlands), atomoxetine (kindly provided by Hemofarm AD, Vrsac, Serbia), diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (DPPO, Sigma-Aldrich, Germany).
Preparation of photoreactive dispersions
Atomoxetine was used as an active ingredient, while PEGDA was used as a photopolymer and DPPO as a photoinitiator in photoreactive dispersions. PEG 400 was used as an excipient to overcome very slow and incomplete drug release from printlets fabricated by photopolymerization using DLP technology. The ratio of PEGDA and PEG 400 was constant in all formulations (3:1), and content of atomoxetine was varied from 5% to 27.5% (Table 1). 30 g of each formulation was prepared by mixing on the magnetic stirrer for 15 minutes, protected from the light.
3D printing of atomoxetine printlets
The templates used for printlets were designed by Autodesk Fusion 360 software and exported as a stereolithography file (.stl) into Creation Workshop X 1.2.1 software. All printlets were fabricated using DLP printer Duplicator 7 (Wanhao, Zhejiang, China). The selected shape was cylinder (8 mm diameter and 2 mm height). Printlets containing 5.00% of atomoxetine were printed with exposure time 5 s, while printlets containing 12.50%, 20.00%, and 27.50% were printed with exposure time 10 s because it was not possible to print more than 1 printlet with exposure time 5 s. All printlets were fabricated without bottom layers, and with layer thickness 0.1 mm.
Determination of mass, dimension and tensile strength of printlets
Mass was determined on 20 printlets, and dimension (digital caliper, Vogel, Germany) was determined on 10 printlets for each formulation. Tensile strength of all formulations was calculated according to the following equation [3]:
σx=2F/πDt
Where:
σx is the tensile strength; F is the tablet breaking force (load); D and t are the diameter and thickness of printlets, respectively.
In vitro drug release testing
Atomoxetine dissolution rate from 3D printlets was tested using USP IV (Flow-through cell, CE7 smart, Sotax, Switzerland) apparatus. Three printlets of each formulation were tested in 250 ml of distilled water at 37±0.5 °C, with a flow rate of 8 ml per minute during 8 h. The amount of dissolved atomoxetine was determined by UV/VIS spectrophotometry at 270 nm (Evolution 300, Thermo Fisher Scientific, Cambridge).
RESULTS AND DISCUSSION
3D printing process
Printlets containing four different amounts of atomoxetine were successfully produced using photoreactive dispersions by the DLP printer. Achieved doses of atomoxetine in printlets were 5.84±0.54 mg, 20.24±0.82 mg, 32.46±1.69 mg and 58.08±3.09 mg, which is a wide range of doses that allow personalization of therapy. Also, total printing time for 10 printlets was 5 and 7 minutes, for exposition time 5 s and 10 s, respectively, which is significantly shorter than printing time in other 3D printing technologies.
Mass, dimension and tensile strength of printlets
Mass, diameter and thickness are shown in Table 2, while tensile strengths of all formulations are shown in Figure 1.
The increase in the atomoxetine content led to the fabrication of printlets with a higher mass and dimensions, due to the higher proportion of atomoxetine particles that were not dissolved in photoreactive mixture and their scattering phenomena in the light beam.
Increasing content of active ingredient led to higher tensile strength of printlets, and all formulations had tensile strength around 1 MPa, which can be sufficient for small batches [4].
Dissolution profiles
Dissolution profiles of formulations containing different content of atomoxetine are shown in Figure 2. Only from formulation A1 more than 80% of atomoxetine was released after 2 h, which can be a consequence of shorter exposition time set during the printing for this formulation, while formulations A2-A4 overlapped during the first hour of the test and achieved sustained release during 8h. After 8h, 88.94%, 79.77%, 77.53% and 72.54% of atomoxetine were released from formulations A1, A2, A3, and A4, respectively.
CONCLUSION
The possibility of successful 3D DLP printing of the printlets using the active ingredient dispersed in the photopolymer mixture, with optimization of printing process parameters for rapid printlet production, has been demonstrated. Printlets with higher content of dispersed atomoxetine have shown decreased drug release rate after 8h, with increasing tensile strength, mass, and dimensions, due to interactions with the light beam.
PB  - International Association for Pharmaceutical Technology, Mainz, Germany
C3  - 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
T1  - Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology
SP  - 1
EP  - 2
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5325
ER  - 

@conference{
author = "Krkobabić, Mirjana and Pešić, Nikola and Boljević, Gordana and Medarević, Đorđe and Ibrić, Svetlana",
year = "2021",
abstract = "INTRODUCTION
Application of the 3D printing in pharmacy make possible production of small batches of solid dosage forms for oral administration (printlets) with different dose and release characteristics that can be customized to specific patient needs [1]. Digital light processing (DLP), one type of 3D printing technology, is based on a UV-triggered localized photopolymerization process of liquid resins [2]. The aim of this study was 3D printing from photoreactive dispersions with different amounts of solid phase and characterization of obtained printlets.
MATERIALS
Different photoreactive dispersions were prepared from poly(ethylene glycol) diacrylate 700 (PEGDA 700, Sigma-Aldrich, Japan), poly(ethylene glycol) 400 (PEG 400, Fagron, Netherlands), atomoxetine (kindly provided by Hemofarm AD, Vrsac, Serbia), diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (DPPO, Sigma-Aldrich, Germany).
Preparation of photoreactive dispersions
Atomoxetine was used as an active ingredient, while PEGDA was used as a photopolymer and DPPO as a photoinitiator in photoreactive dispersions. PEG 400 was used as an excipient to overcome very slow and incomplete drug release from printlets fabricated by photopolymerization using DLP technology. The ratio of PEGDA and PEG 400 was constant in all formulations (3:1), and content of atomoxetine was varied from 5% to 27.5% (Table 1). 30 g of each formulation was prepared by mixing on the magnetic stirrer for 15 minutes, protected from the light.
3D printing of atomoxetine printlets
The templates used for printlets were designed by Autodesk Fusion 360 software and exported as a stereolithography file (.stl) into Creation Workshop X 1.2.1 software. All printlets were fabricated using DLP printer Duplicator 7 (Wanhao, Zhejiang, China). The selected shape was cylinder (8 mm diameter and 2 mm height). Printlets containing 5.00% of atomoxetine were printed with exposure time 5 s, while printlets containing 12.50%, 20.00%, and 27.50% were printed with exposure time 10 s because it was not possible to print more than 1 printlet with exposure time 5 s. All printlets were fabricated without bottom layers, and with layer thickness 0.1 mm.
Determination of mass, dimension and tensile strength of printlets
Mass was determined on 20 printlets, and dimension (digital caliper, Vogel, Germany) was determined on 10 printlets for each formulation. Tensile strength of all formulations was calculated according to the following equation [3]:
σx=2F/πDt
Where:
σx is the tensile strength; F is the tablet breaking force (load); D and t are the diameter and thickness of printlets, respectively.
In vitro drug release testing
Atomoxetine dissolution rate from 3D printlets was tested using USP IV (Flow-through cell, CE7 smart, Sotax, Switzerland) apparatus. Three printlets of each formulation were tested in 250 ml of distilled water at 37±0.5 °C, with a flow rate of 8 ml per minute during 8 h. The amount of dissolved atomoxetine was determined by UV/VIS spectrophotometry at 270 nm (Evolution 300, Thermo Fisher Scientific, Cambridge).
RESULTS AND DISCUSSION
3D printing process
Printlets containing four different amounts of atomoxetine were successfully produced using photoreactive dispersions by the DLP printer. Achieved doses of atomoxetine in printlets were 5.84±0.54 mg, 20.24±0.82 mg, 32.46±1.69 mg and 58.08±3.09 mg, which is a wide range of doses that allow personalization of therapy. Also, total printing time for 10 printlets was 5 and 7 minutes, for exposition time 5 s and 10 s, respectively, which is significantly shorter than printing time in other 3D printing technologies.
Mass, dimension and tensile strength of printlets
Mass, diameter and thickness are shown in Table 2, while tensile strengths of all formulations are shown in Figure 1.
The increase in the atomoxetine content led to the fabrication of printlets with a higher mass and dimensions, due to the higher proportion of atomoxetine particles that were not dissolved in photoreactive mixture and their scattering phenomena in the light beam.
Increasing content of active ingredient led to higher tensile strength of printlets, and all formulations had tensile strength around 1 MPa, which can be sufficient for small batches [4].
Dissolution profiles
Dissolution profiles of formulations containing different content of atomoxetine are shown in Figure 2. Only from formulation A1 more than 80% of atomoxetine was released after 2 h, which can be a consequence of shorter exposition time set during the printing for this formulation, while formulations A2-A4 overlapped during the first hour of the test and achieved sustained release during 8h. After 8h, 88.94%, 79.77%, 77.53% and 72.54% of atomoxetine were released from formulations A1, A2, A3, and A4, respectively.
CONCLUSION
The possibility of successful 3D DLP printing of the printlets using the active ingredient dispersed in the photopolymer mixture, with optimization of printing process parameters for rapid printlet production, has been demonstrated. Printlets with higher content of dispersed atomoxetine have shown decreased drug release rate after 8h, with increasing tensile strength, mass, and dimensions, due to interactions with the light beam.",
publisher = "International Association for Pharmaceutical Technology, Mainz, Germany",
journal = "12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting",
title = "Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology",
pages = "1-2",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5325"
}

Krkobabić, M., Pešić, N., Boljević, G., Medarević, Đ.,& Ibrić, S.. (2021). Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting
International Association for Pharmaceutical Technology, Mainz, Germany., 1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5325

Krkobabić M, Pešić N, Boljević G, Medarević Đ, Ibrić S. Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology. in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting. 2021;:1-2.
https://hdl.handle.net/21.15107/rcub_farfar_5325 .

Krkobabić, Mirjana, Pešić, Nikola, Boljević, Gordana, Medarević, Đorđe, Ibrić, Svetlana, "Characterization of printlets obtained from photoreactive dispersions by digital light processing (DLP) 3D technology" in 12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, 11-14 May 2021, Vienna, Austria, Virtual meeting (2021):1-2,
https://hdl.handle.net/21.15107/rcub_farfar_5325 .

TY  - JOUR
AU  - Ćirić, Ana
AU  - Medarević, Đorđe
AU  - Čalija, Bojan
AU  - Dobričić, Vladimir
AU  - Mitrić, Miodrag
AU  - Đekić, Ljiljana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3524
AB  - This study investigated the combined influence of pH adjusting agent type (hydrochloric, acetic or lactic acid) and initial pH value (3.6, 4.6, and 5.6) on formation of biocompatible chitosan/xanthan polyelectrolyte complexes (PECs), their characteristics in solid state and influence on in vitro ibuprofen release kinetics. Conductivity measurements and rheological characterization revealed generally higher extent of ionic interactions in PEC dispersions comprising acetic acid and at pH 3.6. Acid type and pH affected significantly the yield and particle size (100–250 μm) of the dried PECs. Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) analysis of the solid PECs confirmed exclusively physical (ionic, hydrogen bonds) interactions between chitosan and xanthan gum. PECs prepared with acetic acid at pH 4.6 and 5.6 had enhanced rehydration ability in phosphate buffer pH 7.2, and at PEC-to-drug mass ratio up to 1:2, enabled extended ibuprofen release from hard capsules during 10 h.
PB  - Elsevier B.V.
T2  - International Journal of Biological Macromolecules
T1  - Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics
VL  - 148
SP  - 942
EP  - 955
DO  - 10.1016/j.ijbiomac.2020.01.138
ER  - 

@article{
author = "Ćirić, Ana and Medarević, Đorđe and Čalija, Bojan and Dobričić, Vladimir and Mitrić, Miodrag and Đekić, Ljiljana",
year = "2020",
abstract = "This study investigated the combined influence of pH adjusting agent type (hydrochloric, acetic or lactic acid) and initial pH value (3.6, 4.6, and 5.6) on formation of biocompatible chitosan/xanthan polyelectrolyte complexes (PECs), their characteristics in solid state and influence on in vitro ibuprofen release kinetics. Conductivity measurements and rheological characterization revealed generally higher extent of ionic interactions in PEC dispersions comprising acetic acid and at pH 3.6. Acid type and pH affected significantly the yield and particle size (100–250 μm) of the dried PECs. Differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) analysis of the solid PECs confirmed exclusively physical (ionic, hydrogen bonds) interactions between chitosan and xanthan gum. PECs prepared with acetic acid at pH 4.6 and 5.6 had enhanced rehydration ability in phosphate buffer pH 7.2, and at PEC-to-drug mass ratio up to 1:2, enabled extended ibuprofen release from hard capsules during 10 h.",
publisher = "Elsevier B.V.",
journal = "International Journal of Biological Macromolecules",
title = "Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics",
volume = "148",
pages = "942-955",
doi = "10.1016/j.ijbiomac.2020.01.138"
}

Ćirić, A., Medarević, Đ., Čalija, B., Dobričić, V., Mitrić, M.,& Đekić, L.. (2020). Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics. in International Journal of Biological Macromolecules
Elsevier B.V.., 148, 942-955.
https://doi.org/10.1016/j.ijbiomac.2020.01.138

Ćirić A, Medarević Đ, Čalija B, Dobričić V, Mitrić M, Đekić L. Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics. in International Journal of Biological Macromolecules. 2020;148:942-955.
doi:10.1016/j.ijbiomac.2020.01.138 .

Ćirić, Ana, Medarević, Đorđe, Čalija, Bojan, Dobričić, Vladimir, Mitrić, Miodrag, Đekić, Ljiljana, "Study of chitosan/xanthan gum polyelectrolyte complexes formation, solid state and influence on ibuprofen release kinetics" in International Journal of Biological Macromolecules, 148 (2020):942-955,
https://doi.org/10.1016/j.ijbiomac.2020.01.138 . .

TY  - CONF
AU  - Ćirić, Ana
AU  - Đekić, Ljiljana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5349
AB  - Chitosan/xanthan polyelectrolyte complexes (PECs) are considered promising oral drug delivery carriers due to nontoxicity, biodegradability and can be investigated as potential carriers for extended drug release [1,2]. Ibuprofen has short half-life (t1/2~2 h) and requires frequent administration of immediate release dosage forms [3]. The aim of this study was to investigate the influence of the ibuprofen encapsulation procedure on its in vitro release kinetics. Dried PECs, prepared with chitosan solutions adjusted to pH 4.6 using acetic acid, and ibuprofen dispersed in the xanthan solution before (4.6B) or added after (4.6A) the complexation of polymer aqueous solutions, comprising 100 mg of ibuprofen, were filled into size 0 capsules. In vitro release profiles in the paddle apparatus (50 rpm) (Erweka DT70, Germany) were obtained using 900 ml of phosphate buffer pH 7.2 at 37 ± 1 °C. Both samples showed extended ibuprofen release during 12 h. From 4.6B 100% of ibuprofen was released after 12 h. From 4.6A 66.41 ± 2.14% of substance was released after the same time. Ibuprofen release from the samples followed the Korsmeyer-Peppas kinetics and the release mechanism was a combination of swelling, erosion and diffusion (0.5<n<1). PEC 4.6B showed better control of ibuprofen release and its preparation conditions are considered optimal for controlled extended drug release.
PB  - University of Szeged, Institute of Pharmaceutical Technology and Regulatory Affairs
C3  - II. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science: book of abstracts, 23-24 January 2020, Szeged, Hungary
T1  - Characterization of chitosan/xanthan polyelectrolyte complex carriers: influence of drug encapsulation procedure on in vitro release kinetics
VL  - 2
SP  - 22
EP  - 22
DO  - 10.14232/syrptbrs.2020.op17
ER  - 

@conference{
author = "Ćirić, Ana and Đekić, Ljiljana",
year = "2020",
abstract = "Chitosan/xanthan polyelectrolyte complexes (PECs) are considered promising oral drug delivery carriers due to nontoxicity, biodegradability and can be investigated as potential carriers for extended drug release [1,2]. Ibuprofen has short half-life (t1/2~2 h) and requires frequent administration of immediate release dosage forms [3]. The aim of this study was to investigate the influence of the ibuprofen encapsulation procedure on its in vitro release kinetics. Dried PECs, prepared with chitosan solutions adjusted to pH 4.6 using acetic acid, and ibuprofen dispersed in the xanthan solution before (4.6B) or added after (4.6A) the complexation of polymer aqueous solutions, comprising 100 mg of ibuprofen, were filled into size 0 capsules. In vitro release profiles in the paddle apparatus (50 rpm) (Erweka DT70, Germany) were obtained using 900 ml of phosphate buffer pH 7.2 at 37 ± 1 °C. Both samples showed extended ibuprofen release during 12 h. From 4.6B 100% of ibuprofen was released after 12 h. From 4.6A 66.41 ± 2.14% of substance was released after the same time. Ibuprofen release from the samples followed the Korsmeyer-Peppas kinetics and the release mechanism was a combination of swelling, erosion and diffusion (0.5<n<1). PEC 4.6B showed better control of ibuprofen release and its preparation conditions are considered optimal for controlled extended drug release.",
publisher = "University of Szeged, Institute of Pharmaceutical Technology and Regulatory Affairs",
journal = "II. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science: book of abstracts, 23-24 January 2020, Szeged, Hungary",
title = "Characterization of chitosan/xanthan polyelectrolyte complex carriers: influence of drug encapsulation procedure on in vitro release kinetics",
volume = "2",
pages = "22-22",
doi = "10.14232/syrptbrs.2020.op17"
}

Ćirić, A.,& Đekić, L.. (2020). Characterization of chitosan/xanthan polyelectrolyte complex carriers: influence of drug encapsulation procedure on in vitro release kinetics. in II. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science: book of abstracts, 23-24 January 2020, Szeged, Hungary
University of Szeged, Institute of Pharmaceutical Technology and Regulatory Affairs., 2, 22-22.
https://doi.org/10.14232/syrptbrs.2020.op17

Ćirić A, Đekić L. Characterization of chitosan/xanthan polyelectrolyte complex carriers: influence of drug encapsulation procedure on in vitro release kinetics. in II. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science: book of abstracts, 23-24 January 2020, Szeged, Hungary. 2020;2:22-22.
doi:10.14232/syrptbrs.2020.op17 .

Ćirić, Ana, Đekić, Ljiljana, "Characterization of chitosan/xanthan polyelectrolyte complex carriers: influence of drug encapsulation procedure on in vitro release kinetics" in II. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science: book of abstracts, 23-24 January 2020, Szeged, Hungary, 2 (2020):22-22,
https://doi.org/10.14232/syrptbrs.2020.op17 . .

TY  - THES
AU  - Drašković, Milica
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7514
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22400/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=16614665
UR  - http://nardus.mpn.gov.rs/handle/123456789/17331
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3707
AB  - Oralno-disperzibilne tablete (ODT) i oralno-disperzibilni filmovi (ODF) predstavljajukompleksne formulacije koje su namenjene primeni u ustima, gde se u kontaktu sa salivom,gotovo trenutno raspadaju. Pored zahteva za brzo raspadanje, potrebno je da pokazuju iprihvatljivu mehaničku otpornosti kako bi se obezbedila adekvatna manipulacija tokomproizvodnje i primene leka. Cilj istraživanja je bilo ispitivanje i mehanističko objašnjenjeuticaja različitih faktora formulacije i procesnih parametara na raspadljivost i mehaničkekarakteristike, koji su prepoznati kao kritični atributi kvaliteta ODT/ODF.Dinamička analiza kompakcije i teorija perkolacije primenjene su sa ciljem procenefunkcionalnosti novih, direktno kompresibilnih, koprocesovanih ekscipijenasa dizajniranihposebno za razvoj formulacije ODT. Test na istezanje i oscilatorna reološka merenjasprovedena su u svrhu sveobuhvatne analize uticaja različitih ekscipijenasa (hidrofilnipolimeri, superdezintegratori) i variranja udela plastifikatora na mehanička svojstva ODF,pripremljenih metodom izlivanja. Direktno oblaganje čestica sprovedeno je sa ciljemmaskiranja neprijatnog ukusa ispitivanih lekovitih supstanci, nakon čega je sprovedena in vivoi in vitro procena efikasnosti primenjenog pristupa. Fiziološki zasnovano farmakokinetičkomodelovanje primenjeno je sa ciljem simuliranja in vivo ponašanja ispitivanih preparata iprocene obima apsorpcije lekovite supstance iz odabranih ODT/ODF primenom nedavnorazvijenog prostornog modela apsorpcije i tranzita kroz usnu duplju (OCCATTM).Rezultati sveobuhvatne farmaceutsko-tehnološke karakterizacije i dinamičke analizekompakcije ispitivanih korpocesovanih ekscipijenasa ukazali su na kompleksne odnoseizmeđu osnovnih karakteristika materijala i njihove funkcionalnosti. Uprkos činjenici da sebrzo raspadanje najčešće dovodi u vezu sa lošijom mehaničkom otpornošću tableta, bilo jemoguće formulisati ODT sa visokim udelom lekovitih supstanci (37-67% kofeina, odnosno18-49% ibuprofena) bez narušavanja kritičnih karakteristika kvaliteta (vreme raspadanja < 3mi; zatezna čvrstina > 1 MPa). U slučaju ODF, ispitivani hidrofilni polimeri su obezbediliinkorporiranje 20-25% kofeina, odnosno ibuprofena uz održavanje brzog raspadanja iodgovarajućih mehaničkih svojstava. In vivo i in vitro procenom efikasnosti maskiranja ukusapotvrđena je uspešnost direktnog oblaganja čestica kao metode za maskiranje neprijatnogukusa lekovitih supstanci. Visok stepen korelacije između in vivo i in vitro podataka ukazujeda se modifikovani test dispergovanja lekovitih supstanci u maloj zapremini medijuma možekoristiti kao zamena za in vivo ispitivanja efikasnosti maskiranja ukusa. In silico rezultatisimulacije apsorpcije kofeina, odnosno ibuprofena iz pripremljenih oralno-disperzibilnihfarmaceutskih oblika ukazuju da se nakon primene ispitivanih formulacija može očekivatizanemarljiv obim intraoralne apsorpcije i biološka raspoloživost slična onoj koja se postiženakon primene konvencionalnih peroralnih farmaceutskih oblika sa trenutnim oslobađanjem.
AB  - Novel solid dosage forms, orodispersible tablets (ODTs) and orodispersible films (ODFs), aredeveloped as complex formulations providing fast dosage form disintegration in oral cavitycoupled with adequate mechanical resistance to withstand manipulation during manufactureand drug administration. The aim of the study was to investigate and mechanistically explainthe influence of different formulation factors and process parameters on dosage formdisintegration and mechanical properties identified as ODT/ODF critical quality attributes(CQAs).Dynamic compaction analysis and percolation theory were employed in order to explorematerial properties of novel, directly compressible coprocessed excipients designedspecifically for ODT formulation. Tensile tests and oscillatory rheology were employed forcomprehensive evaluation of various excipients selection, including film-forming polymers,superdisintegrants and plasticizer load on mechanical properties of ODFs prepared by solventcasting method. Direct drug coating was applied with the aim to mask unpleasant taste of theinvestigated active substances, accompanied with the in vivo and in vitro evaluation of tastemasking effectiveness. Physiologically based pharmacokinetic modeling has been performedwith the aim to simulate in vivo dosage form performance and predict drug absorption fromthe investigated ODT/ODF using recently developed Oral Cavity Compartmental Absorption& Transit (OCCATTM) model.Comprehensive pharmaceutical-technological evaluation and dynamic compaction analysis ofthe investigated coprocessed excipients revealed complex relation between fundamentalmaterial characteristics and their functionality. Despite the fact that fast disintegration is,generally, associated with poor mechanical resistance of the solid dosage form, it was possibleto obtain ODTs with high drug load (37-67% in the case of caffeine, and 18-49% in the caseof ibuprofen) without compromising the targeted CQAs (i.e. the obtained disintegration timewas less than 3 min, and tensile strength higher than 1 MPa). In the case of ODFs, theinvestigated film-forming agents have provided incorporation of 20-25% of caffeine, oribuprofen load while maintaining fast disintegration and suitable mechanical properties. Invivo and in vitro evaluation of drug taste masking effectiveness indicate usefulness of directdrug coating. Strong correlation between in vivo and in vitro data implicate that small-volumedissolution method may be used as a surrogate for human panel taste-masking assessment, inthe case of physical taste-masking approach application. Outcomes of physiologically basedpharmacokinetic modeling indicate that intraoral drug absorption from the investigatedODF/ODT would be negligible and that administration of orodispersible drug dosage formswould provide similar bioavailability as conventional immediate release dosage forms.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Formulacija i karakterizacija oralno-disperzibilnih farmaceutskih oblika sa visokim udelom lekovitih supstanci: doprinos mehanističkom razumevanju sistema
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17331
ER  - 

@phdthesis{
author = "Drašković, Milica",
year = "2020",
abstract = "Oralno-disperzibilne tablete (ODT) i oralno-disperzibilni filmovi (ODF) predstavljajukompleksne formulacije koje su namenjene primeni u ustima, gde se u kontaktu sa salivom,gotovo trenutno raspadaju. Pored zahteva za brzo raspadanje, potrebno je da pokazuju iprihvatljivu mehaničku otpornosti kako bi se obezbedila adekvatna manipulacija tokomproizvodnje i primene leka. Cilj istraživanja je bilo ispitivanje i mehanističko objašnjenjeuticaja različitih faktora formulacije i procesnih parametara na raspadljivost i mehaničkekarakteristike, koji su prepoznati kao kritični atributi kvaliteta ODT/ODF.Dinamička analiza kompakcije i teorija perkolacije primenjene su sa ciljem procenefunkcionalnosti novih, direktno kompresibilnih, koprocesovanih ekscipijenasa dizajniranihposebno za razvoj formulacije ODT. Test na istezanje i oscilatorna reološka merenjasprovedena su u svrhu sveobuhvatne analize uticaja različitih ekscipijenasa (hidrofilnipolimeri, superdezintegratori) i variranja udela plastifikatora na mehanička svojstva ODF,pripremljenih metodom izlivanja. Direktno oblaganje čestica sprovedeno je sa ciljemmaskiranja neprijatnog ukusa ispitivanih lekovitih supstanci, nakon čega je sprovedena in vivoi in vitro procena efikasnosti primenjenog pristupa. Fiziološki zasnovano farmakokinetičkomodelovanje primenjeno je sa ciljem simuliranja in vivo ponašanja ispitivanih preparata iprocene obima apsorpcije lekovite supstance iz odabranih ODT/ODF primenom nedavnorazvijenog prostornog modela apsorpcije i tranzita kroz usnu duplju (OCCATTM).Rezultati sveobuhvatne farmaceutsko-tehnološke karakterizacije i dinamičke analizekompakcije ispitivanih korpocesovanih ekscipijenasa ukazali su na kompleksne odnoseizmeđu osnovnih karakteristika materijala i njihove funkcionalnosti. Uprkos činjenici da sebrzo raspadanje najčešće dovodi u vezu sa lošijom mehaničkom otpornošću tableta, bilo jemoguće formulisati ODT sa visokim udelom lekovitih supstanci (37-67% kofeina, odnosno18-49% ibuprofena) bez narušavanja kritičnih karakteristika kvaliteta (vreme raspadanja < 3mi; zatezna čvrstina > 1 MPa). U slučaju ODF, ispitivani hidrofilni polimeri su obezbediliinkorporiranje 20-25% kofeina, odnosno ibuprofena uz održavanje brzog raspadanja iodgovarajućih mehaničkih svojstava. In vivo i in vitro procenom efikasnosti maskiranja ukusapotvrđena je uspešnost direktnog oblaganja čestica kao metode za maskiranje neprijatnogukusa lekovitih supstanci. Visok stepen korelacije između in vivo i in vitro podataka ukazujeda se modifikovani test dispergovanja lekovitih supstanci u maloj zapremini medijuma možekoristiti kao zamena za in vivo ispitivanja efikasnosti maskiranja ukusa. In silico rezultatisimulacije apsorpcije kofeina, odnosno ibuprofena iz pripremljenih oralno-disperzibilnihfarmaceutskih oblika ukazuju da se nakon primene ispitivanih formulacija može očekivatizanemarljiv obim intraoralne apsorpcije i biološka raspoloživost slična onoj koja se postiženakon primene konvencionalnih peroralnih farmaceutskih oblika sa trenutnim oslobađanjem., Novel solid dosage forms, orodispersible tablets (ODTs) and orodispersible films (ODFs), aredeveloped as complex formulations providing fast dosage form disintegration in oral cavitycoupled with adequate mechanical resistance to withstand manipulation during manufactureand drug administration. The aim of the study was to investigate and mechanistically explainthe influence of different formulation factors and process parameters on dosage formdisintegration and mechanical properties identified as ODT/ODF critical quality attributes(CQAs).Dynamic compaction analysis and percolation theory were employed in order to explorematerial properties of novel, directly compressible coprocessed excipients designedspecifically for ODT formulation. Tensile tests and oscillatory rheology were employed forcomprehensive evaluation of various excipients selection, including film-forming polymers,superdisintegrants and plasticizer load on mechanical properties of ODFs prepared by solventcasting method. Direct drug coating was applied with the aim to mask unpleasant taste of theinvestigated active substances, accompanied with the in vivo and in vitro evaluation of tastemasking effectiveness. Physiologically based pharmacokinetic modeling has been performedwith the aim to simulate in vivo dosage form performance and predict drug absorption fromthe investigated ODT/ODF using recently developed Oral Cavity Compartmental Absorption& Transit (OCCATTM) model.Comprehensive pharmaceutical-technological evaluation and dynamic compaction analysis ofthe investigated coprocessed excipients revealed complex relation between fundamentalmaterial characteristics and their functionality. Despite the fact that fast disintegration is,generally, associated with poor mechanical resistance of the solid dosage form, it was possibleto obtain ODTs with high drug load (37-67% in the case of caffeine, and 18-49% in the caseof ibuprofen) without compromising the targeted CQAs (i.e. the obtained disintegration timewas less than 3 min, and tensile strength higher than 1 MPa). In the case of ODFs, theinvestigated film-forming agents have provided incorporation of 20-25% of caffeine, oribuprofen load while maintaining fast disintegration and suitable mechanical properties. Invivo and in vitro evaluation of drug taste masking effectiveness indicate usefulness of directdrug coating. Strong correlation between in vivo and in vitro data implicate that small-volumedissolution method may be used as a surrogate for human panel taste-masking assessment, inthe case of physical taste-masking approach application. Outcomes of physiologically basedpharmacokinetic modeling indicate that intraoral drug absorption from the investigatedODF/ODT would be negligible and that administration of orodispersible drug dosage formswould provide similar bioavailability as conventional immediate release dosage forms.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Formulacija i karakterizacija oralno-disperzibilnih farmaceutskih oblika sa visokim udelom lekovitih supstanci: doprinos mehanističkom razumevanju sistema",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17331"
}

Drašković, M.. (2020). Formulacija i karakterizacija oralno-disperzibilnih farmaceutskih oblika sa visokim udelom lekovitih supstanci: doprinos mehanističkom razumevanju sistema. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17331

Drašković M. Formulacija i karakterizacija oralno-disperzibilnih farmaceutskih oblika sa visokim udelom lekovitih supstanci: doprinos mehanističkom razumevanju sistema. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17331 .

Drašković, Milica, "Formulacija i karakterizacija oralno-disperzibilnih farmaceutskih oblika sa visokim udelom lekovitih supstanci: doprinos mehanističkom razumevanju sistema" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17331 .

TY  - JOUR
AU  - Krivokapić, Jovana
AU  - Ivanović, Jasna
AU  - Đuriš, Jelena
AU  - Medarević, Đorđe
AU  - Potpara, Zorica
AU  - Maksimović, Zoran
AU  - Ibrić, Svetlana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3621
AB  - The objective of this work was to study the relation between the manufacturing conditions of microcrystalline cellulose (MCC), its physicochemical properties and its tableting behavior. Two different preparation procedures were used to produce MCC from wheat straw, utilizing an acid hydrolysis method, either using only sulfuric acid or combination of sulfuric and hydrochloric acid. The tableting behavior of obtained MCC samples and mixtures of MCC with ibuprofen was studied using a dynamic powder compaction analyzer. It was observed that some of the obtained MCC samples showed better flowing properties than commercially available Vivapur® PH101 and also very high values of tensile strength, solid fraction and elastic recovery. This can be linked with its good compaction behavior, but on the other hand it can cause problems with the disintegration of the tablets. In mixtures with ibuprofen, MCC samples showed lower values of tensile strength, while on the other hand elastic recovery did not seem to be much affected, still exhibiting very high values. According to the obtained results, it can be concluded that MCC obtained from the agricultural waste could have satisfactory properties for tablet preparation by the direct compression method. Further studies are needed to optimize process conditions in order to achieve better physicochemical characteristics, especially in terms of elastic recovery.
PB  - Elsevier B.V.
T2  - Saudi Pharmaceutical Journal
T1  - Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press
VL  - 2
SP  - 710
EP  - 718
DO  - 10.1016/j.jsps.2020.04.013
ER  - 

@article{
author = "Krivokapić, Jovana and Ivanović, Jasna and Đuriš, Jelena and Medarević, Đorđe and Potpara, Zorica and Maksimović, Zoran and Ibrić, Svetlana",
year = "2020",
abstract = "The objective of this work was to study the relation between the manufacturing conditions of microcrystalline cellulose (MCC), its physicochemical properties and its tableting behavior. Two different preparation procedures were used to produce MCC from wheat straw, utilizing an acid hydrolysis method, either using only sulfuric acid or combination of sulfuric and hydrochloric acid. The tableting behavior of obtained MCC samples and mixtures of MCC with ibuprofen was studied using a dynamic powder compaction analyzer. It was observed that some of the obtained MCC samples showed better flowing properties than commercially available Vivapur® PH101 and also very high values of tensile strength, solid fraction and elastic recovery. This can be linked with its good compaction behavior, but on the other hand it can cause problems with the disintegration of the tablets. In mixtures with ibuprofen, MCC samples showed lower values of tensile strength, while on the other hand elastic recovery did not seem to be much affected, still exhibiting very high values. According to the obtained results, it can be concluded that MCC obtained from the agricultural waste could have satisfactory properties for tablet preparation by the direct compression method. Further studies are needed to optimize process conditions in order to achieve better physicochemical characteristics, especially in terms of elastic recovery.",
publisher = "Elsevier B.V.",
journal = "Saudi Pharmaceutical Journal",
title = "Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press",
volume = "2",
pages = "710-718",
doi = "10.1016/j.jsps.2020.04.013"
}

Krivokapić, J., Ivanović, J., Đuriš, J., Medarević, Đ., Potpara, Z., Maksimović, Z.,& Ibrić, S.. (2020). Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press. in Saudi Pharmaceutical Journal
Elsevier B.V.., 2, 710-718.
https://doi.org/10.1016/j.jsps.2020.04.013

Krivokapić J, Ivanović J, Đuriš J, Medarević Đ, Potpara Z, Maksimović Z, Ibrić S. Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press. in Saudi Pharmaceutical Journal. 2020;2:710-718.
doi:10.1016/j.jsps.2020.04.013 .

Krivokapić, Jovana, Ivanović, Jasna, Đuriš, Jelena, Medarević, Đorđe, Potpara, Zorica, Maksimović, Zoran, Ibrić, Svetlana, "Tableting properties of microcrystalline cellulose obtained from wheat straw measured with a single punch bench top tablet press" in Saudi Pharmaceutical Journal, 2 (2020):710-718,
https://doi.org/10.1016/j.jsps.2020.04.013 . .

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 . .

TY  - JOUR
AU  - Milanović, Ana
AU  - Aleksić, Ivana
AU  - Ibrić, Svetlana
AU  - Parojčić, Jelena
AU  - Cvijić, Sandra
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3508
AB  - Hot-melt coating (HMC) has been recognized as a promising technique in the production of solid dosage forms e.g., HMC of granules can be applied prior to compression in order to obtain modified drug release or taste masking. However, tableting properties of HMC granules have not been studied yet. In this work, we explored the influence of the lipid coating on granules tableting properties, and assessed quality attributes of the obtained tablets. Paracetamol granules, previously coated with the lipid excipient Precirol® ATO 5 using a hot-melt coating technique in modified fluidized-bed system, were evaluated in terms of work of compression, elastic recovery, tablets tensile strength, detachment stress and ejection stress. Regarding the product quality, tablets content uniformity, friability, disintegration time and drug release properties were tested. Our results demonstrated that tablets made of coated granules exhibited more pronounced elastic behaviour, and increased tensile strength in comparison to tablets made of uncoated granules, suggesting that lipid coating promotes elastic deformation and forms lipid matrix within the tablets. Additionally, low detachment and ejection stresses for tablets made of HMC granules indicated no need to add lubricant prior to tableting process. Evaluation of tablets properties revealed that tablets friability was not influenced by the presence of lipid coating on the compressed granules. However, formation of lipid matrix within the tablets made of HMC granules resulted in prolonged tablet disintegration time, and sustained drug release. Moreover, the performance of lipid matrix tablets, in terms of drug dissolution rate, was relatively insensitive to compression pressure variations in 104–173 MPa range. The obtained results indicate that tableting of HMC granules is a promising technique to obtain sustained release lipid matrix tablets of suitable pharmaceutical-technical properties.
PB  - Elsevier B.V.
T2  - European Journal of Pharmaceutical Sciences
T1  - Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets
VL  - 142
DO  - 10.1016/j.ejps.2019.105121
ER  - 

@article{
author = "Milanović, Ana and Aleksić, Ivana and Ibrić, Svetlana and Parojčić, Jelena and Cvijić, Sandra",
year = "2020",
abstract = "Hot-melt coating (HMC) has been recognized as a promising technique in the production of solid dosage forms e.g., HMC of granules can be applied prior to compression in order to obtain modified drug release or taste masking. However, tableting properties of HMC granules have not been studied yet. In this work, we explored the influence of the lipid coating on granules tableting properties, and assessed quality attributes of the obtained tablets. Paracetamol granules, previously coated with the lipid excipient Precirol® ATO 5 using a hot-melt coating technique in modified fluidized-bed system, were evaluated in terms of work of compression, elastic recovery, tablets tensile strength, detachment stress and ejection stress. Regarding the product quality, tablets content uniformity, friability, disintegration time and drug release properties were tested. Our results demonstrated that tablets made of coated granules exhibited more pronounced elastic behaviour, and increased tensile strength in comparison to tablets made of uncoated granules, suggesting that lipid coating promotes elastic deformation and forms lipid matrix within the tablets. Additionally, low detachment and ejection stresses for tablets made of HMC granules indicated no need to add lubricant prior to tableting process. Evaluation of tablets properties revealed that tablets friability was not influenced by the presence of lipid coating on the compressed granules. However, formation of lipid matrix within the tablets made of HMC granules resulted in prolonged tablet disintegration time, and sustained drug release. Moreover, the performance of lipid matrix tablets, in terms of drug dissolution rate, was relatively insensitive to compression pressure variations in 104–173 MPa range. The obtained results indicate that tableting of HMC granules is a promising technique to obtain sustained release lipid matrix tablets of suitable pharmaceutical-technical properties.",
publisher = "Elsevier B.V.",
journal = "European Journal of Pharmaceutical Sciences",
title = "Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets",
volume = "142",
doi = "10.1016/j.ejps.2019.105121"
}

Milanović, A., Aleksić, I., Ibrić, S., Parojčić, J.,& Cvijić, S.. (2020). Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets. in European Journal of Pharmaceutical Sciences
Elsevier B.V.., 142.
https://doi.org/10.1016/j.ejps.2019.105121

Milanović A, Aleksić I, Ibrić S, Parojčić J, Cvijić S. Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets. in European Journal of Pharmaceutical Sciences. 2020;142.
doi:10.1016/j.ejps.2019.105121 .

Milanović, Ana, Aleksić, Ivana, Ibrić, Svetlana, Parojčić, Jelena, Cvijić, Sandra, "Tableting of hot-melt coated paracetamol granules: Material tableting properties and quality characteristics of the obtained tablets" in European Journal of Pharmaceutical Sciences, 142 (2020),
https://doi.org/10.1016/j.ejps.2019.105121 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Vardaka, Elisavet
AU  - Mitrić, Miodrag
AU  - Nikolakakis, Ioannis
AU  - Kachrimanis, Kyriakos
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3497
AB  - Nanocrystal formation for the dissolution enhancement of glimepiride was attempted
by wet media milling. Di erent stabilizers were tested and the obtained nanosuspensions were
solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility
by dynamic light scattering, physicochemical properties by di erential scanning calorimetry (DSC),
FT-IR spectroscopy, powder X-ray di raction (PXRD), and scanning electron microcopy (SEM), as
well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in
order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with
narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603
stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals
during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic
transformations during processing, and that the milling process induces changes in the hydrogen
bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed
the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD
analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the
important influence of the stabilizer on the dissolution rate of the nanocrystals.
PB  - MDPI
T2  - Pharmaceutics
T1  - Insight into the formation of glimepiride nanocrystals by wet media milling
VL  - 12
IS  - 1
DO  - 10.3390/pharmaceutics12010053
ER  - 

@article{
author = "Medarević, Đorđe and Ibrić, Svetlana and Vardaka, Elisavet and Mitrić, Miodrag and Nikolakakis, Ioannis and Kachrimanis, Kyriakos",
year = "2020",
abstract = "Nanocrystal formation for the dissolution enhancement of glimepiride was attempted
by wet media milling. Di erent stabilizers were tested and the obtained nanosuspensions were
solidified by spray drying in presence of mannitol, and characterized regarding their redispersibility
by dynamic light scattering, physicochemical properties by di erential scanning calorimetry (DSC),
FT-IR spectroscopy, powder X-ray di raction (PXRD), and scanning electron microcopy (SEM), as
well as dissolution rate. Lattice energy frameworks combined with topology analysis were used in
order to gain insight into the mechanisms of particle fracture. It was found that nanosuspensions with
narrow size distribution can be obtained in presence of poloxamer 188, HPC-SL and Pharmacoat® 603
stabilizers, with poloxamer giving poor redispersibility due to melting and sticking of nanocrystals
during spray drying. DSC and FT-IR studies showed that glimepiride does not undergo polymorphic
transformations during processing, and that the milling process induces changes in the hydrogen
bonding patterns of glimepiride crystals. Lattice energy framework and topology analysis revealed
the existence of a possible slip plane on the (101) surface, which was experimentally verified by PXRD
analysis. Dissolution testing proved the superior performance of nanocrystals, and emphasized the
important influence of the stabilizer on the dissolution rate of the nanocrystals.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Insight into the formation of glimepiride nanocrystals by wet media milling",
volume = "12",
number = "1",
doi = "10.3390/pharmaceutics12010053"
}

Medarević, Đ., Ibrić, S., Vardaka, E., Mitrić, M., Nikolakakis, I.,& Kachrimanis, K.. (2020). Insight into the formation of glimepiride nanocrystals by wet media milling. in Pharmaceutics
MDPI., 12(1).
https://doi.org/10.3390/pharmaceutics12010053

Medarević Đ, Ibrić S, Vardaka E, Mitrić M, Nikolakakis I, Kachrimanis K. Insight into the formation of glimepiride nanocrystals by wet media milling. in Pharmaceutics. 2020;12(1).
doi:10.3390/pharmaceutics12010053 .

Medarević, Đorđe, Ibrić, Svetlana, Vardaka, Elisavet, Mitrić, Miodrag, Nikolakakis, Ioannis, Kachrimanis, Kyriakos, "Insight into the formation of glimepiride nanocrystals by wet media milling" in Pharmaceutics, 12, no. 1 (2020),
https://doi.org/10.3390/pharmaceutics12010053 . .

TY  - JOUR
AU  - Gatarić, Biljana
AU  - Parojčić, Jelena
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3488
AB  - Drug absorption is a complex process governed by a number of interrelatedphysicochemical, biopharmaceutical, and pharmacokinetic factors. In order to explore complexrelationships among these factors, multivariate exploratory analysis was performed on thedataset of drugs with diverse bioperformance. The investigated dataset included subset of drugsfor which bioequivalence between solid dosage form and oral solution has been reported, andsubset of drugs described in the literature as low solubility/low permeability compounds.Discriminatory power of hierarchical clustering on principal components was somewhat higherwhen applied on the data subsets of drugs with similar bioperformance, while analysis of theintegrated dataset indicated existence of two groups of drugs with the boundaries reflected in Peffvalue of approximately 2 × 10−4cm/s and Fa and Fm values higher than 85% and 50%,respectively. Majority of the investigated drugs within the integrated dataset were grouped withintheir initial subset indicating that overall drug bioperformance is closely related to itsphysicochemical, biopharmaceutical and pharmacokinetic properties. Classification modelsconstructed using the random forest (RF) and support vector machine with polynomial kernelfunction were able to predict food effect based on drug dose/solubility ratio (D/S), effectivepermeability (Peff), percent of dose metabolized (Fm), and elimination half-life (τ1/2). Althoughboth models performed well during training and testing, only RF kept satisfying performancewhen applied on the external dataset (kappa value > 0.4). The results obtained indicate that datamining can be employed as useful tool in biopharmaceutical drug characterization which meritsfurther investigation
PB  - Springer International Publishing
T2  - APPS Journal
T1  - An Investigation into the Factors Governing Drug Absorption and Food Effect Prediction Based on Data Mining Methodology
VL  - 22
IS  - 1
DO  - 10.1208/s12248-019-0394-y
ER  - 

@article{
author = "Gatarić, Biljana and Parojčić, Jelena",
year = "2020",
abstract = "Drug absorption is a complex process governed by a number of interrelatedphysicochemical, biopharmaceutical, and pharmacokinetic factors. In order to explore complexrelationships among these factors, multivariate exploratory analysis was performed on thedataset of drugs with diverse bioperformance. The investigated dataset included subset of drugsfor which bioequivalence between solid dosage form and oral solution has been reported, andsubset of drugs described in the literature as low solubility/low permeability compounds.Discriminatory power of hierarchical clustering on principal components was somewhat higherwhen applied on the data subsets of drugs with similar bioperformance, while analysis of theintegrated dataset indicated existence of two groups of drugs with the boundaries reflected in Peffvalue of approximately 2 × 10−4cm/s and Fa and Fm values higher than 85% and 50%,respectively. Majority of the investigated drugs within the integrated dataset were grouped withintheir initial subset indicating that overall drug bioperformance is closely related to itsphysicochemical, biopharmaceutical and pharmacokinetic properties. Classification modelsconstructed using the random forest (RF) and support vector machine with polynomial kernelfunction were able to predict food effect based on drug dose/solubility ratio (D/S), effectivepermeability (Peff), percent of dose metabolized (Fm), and elimination half-life (τ1/2). Althoughboth models performed well during training and testing, only RF kept satisfying performancewhen applied on the external dataset (kappa value > 0.4). The results obtained indicate that datamining can be employed as useful tool in biopharmaceutical drug characterization which meritsfurther investigation",
publisher = "Springer International Publishing",
journal = "APPS Journal",
title = "An Investigation into the Factors Governing Drug Absorption and Food Effect Prediction Based on Data Mining Methodology",
volume = "22",
number = "1",
doi = "10.1208/s12248-019-0394-y"
}

Gatarić, B.,& Parojčić, J.. (2020). An Investigation into the Factors Governing Drug Absorption and Food Effect Prediction Based on Data Mining Methodology. in APPS Journal
Springer International Publishing., 22(1).
https://doi.org/10.1208/s12248-019-0394-y

Gatarić B, Parojčić J. An Investigation into the Factors Governing Drug Absorption and Food Effect Prediction Based on Data Mining Methodology. in APPS Journal. 2020;22(1).
doi:10.1208/s12248-019-0394-y .

Gatarić, Biljana, Parojčić, Jelena, "An Investigation into the Factors Governing Drug Absorption and Food Effect Prediction Based on Data Mining Methodology" in APPS Journal, 22, no. 1 (2020),
https://doi.org/10.1208/s12248-019-0394-y . .

TY  - CONF
AU  - Đuriš, Jelena
AU  - Milovanović, Stoja
AU  - Medarević, Đorđe
AU  - Dobričić, Vladimir
AU  - Ibrić, Svetlana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5483
AB  - Formulation of solid dispersions is one of the most feasible strategies for overcoming the poor
drugs’ solubility – one of the major issues affecting drug bioavailability and therapeutic outcomes.
Since traditional methods used for preparation of solid dispersions often require usage of organic
solvents, it is of great importance to seek for more environment-friendly methods. It has been
demonstrated that supercritical (sc) CO2 may be effectively utilized for dispersion of drugs into the
suitable carrier (polymer), thus obtaining solid dispersions with the improved drug dissolution rate.
The aim of the presented study was to investigate the potential of scCO2 for preparation of poorly
soluble antihypertensive drugs (carvedilol and valsartan) solid dispersions in the conventional
pharmaceutical polymers (polyvinilypyrolidone-PVP and hypromellose-HPMC). Prepared solid
dispersions were characterized by scanning electron microscopy, differential scanning calorimetry
and Fourier-transform infrared spectroscopy; their porosity and density were determined and drug
dissolution rate was assessed and compared to the results obtained from solid dispersions prepared
by the traditional solvent casting method. Selected samples were tested for their tableting properties
as well. It has been demonstrated that scCO2 may be successfully applied for preparation of
carvedilol or valsartan solid dispersions with the improved drug dissolution rate. Further
characterization revealed the nature of interactions between the drugs and selected polymers. Due
to the low density (and high porosity), some of the prepared solid dispersions may be used for
further development of the floating dosage forms. It has also been demonstrated that some of the
prepared dispersions have excellent compressibility and compactibility, which is of great
importance for further development of solid dosage forms. The obtained results provide framework
for further development of environment-friendly methods in pharmaceutical development and
production.
PB  - Materials Research Society of Serbia
PB  - International Institute for the Science of Sintering
C3  - Twenty-first Annual Conference YUCOMAT 2019 & Eleventh World Round Table Conference on Sintering WRTCS 2019, September 2-6, 2019, Herceg Novi, Montenegro
T1  - Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions
SP  - 71
EP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5483
ER  - 

@conference{
author = "Đuriš, Jelena and Milovanović, Stoja and Medarević, Đorđe and Dobričić, Vladimir and Ibrić, Svetlana",
year = "2019",
abstract = "Formulation of solid dispersions is one of the most feasible strategies for overcoming the poor
drugs’ solubility – one of the major issues affecting drug bioavailability and therapeutic outcomes.
Since traditional methods used for preparation of solid dispersions often require usage of organic
solvents, it is of great importance to seek for more environment-friendly methods. It has been
demonstrated that supercritical (sc) CO2 may be effectively utilized for dispersion of drugs into the
suitable carrier (polymer), thus obtaining solid dispersions with the improved drug dissolution rate.
The aim of the presented study was to investigate the potential of scCO2 for preparation of poorly
soluble antihypertensive drugs (carvedilol and valsartan) solid dispersions in the conventional
pharmaceutical polymers (polyvinilypyrolidone-PVP and hypromellose-HPMC). Prepared solid
dispersions were characterized by scanning electron microscopy, differential scanning calorimetry
and Fourier-transform infrared spectroscopy; their porosity and density were determined and drug
dissolution rate was assessed and compared to the results obtained from solid dispersions prepared
by the traditional solvent casting method. Selected samples were tested for their tableting properties
as well. It has been demonstrated that scCO2 may be successfully applied for preparation of
carvedilol or valsartan solid dispersions with the improved drug dissolution rate. Further
characterization revealed the nature of interactions between the drugs and selected polymers. Due
to the low density (and high porosity), some of the prepared solid dispersions may be used for
further development of the floating dosage forms. It has also been demonstrated that some of the
prepared dispersions have excellent compressibility and compactibility, which is of great
importance for further development of solid dosage forms. The obtained results provide framework
for further development of environment-friendly methods in pharmaceutical development and
production.",
publisher = "Materials Research Society of Serbia, International Institute for the Science of Sintering",
journal = "Twenty-first Annual Conference YUCOMAT 2019 & Eleventh World Round Table Conference on Sintering WRTCS 2019, September 2-6, 2019, Herceg Novi, Montenegro",
title = "Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5483"
}

Đuriš, J., Milovanović, S., Medarević, Đ., Dobričić, V.,& Ibrić, S.. (2019). Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions. in Twenty-first Annual Conference YUCOMAT 2019 & Eleventh World Round Table Conference on Sintering WRTCS 2019, September 2-6, 2019, Herceg Novi, Montenegro
Materials Research Society of Serbia., 71-71.
https://hdl.handle.net/21.15107/rcub_farfar_5483

Đuriš J, Milovanović S, Medarević Đ, Dobričić V, Ibrić S. Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions. in Twenty-first Annual Conference YUCOMAT 2019 & Eleventh World Round Table Conference on Sintering WRTCS 2019, September 2-6, 2019, Herceg Novi, Montenegro. 2019;:71-71.
https://hdl.handle.net/21.15107/rcub_farfar_5483 .

Đuriš, Jelena, Milovanović, Stoja, Medarević, Đorđe, Dobričić, Vladimir, Ibrić, Svetlana, "Supercritical CO2 utilization in preparation of poorly soluble drugs solid dispersions" in Twenty-first Annual Conference YUCOMAT 2019 & Eleventh World Round Table Conference on Sintering WRTCS 2019, September 2-6, 2019, Herceg Novi, Montenegro (2019):71-71,
https://hdl.handle.net/21.15107/rcub_farfar_5483 .

TY  - CONF
AU  - Ćirić, Ana
AU  - Đekić, Ljiljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5368
AB  - Polielektrolitni kompleksi (PEC) nastaju uspostavljanjem jonskih interakcija između polimera
pri pH oko njihovih pKa. Formiranje i kapacitet PEC za rehidrataciju u fiziološkim tečnostima,
koje može uticati na mehanizam i brzinu oslobađanja aktivne supstance, može zavisiti od
pH i prirode medijuma. Cilj rada je ispitivanje uticaja pH medijuma i upotrebljene kiseline na
rehidrataciju čvrstih PEC hitozana i ksantana. Pripremljeni hidrogelovi tipa PEC ksantana i
hitozana pri pH 3,6; 4,6 i 5,6, upotrebom hlorovodonične (HK) i sirćetne (SK) kiseline su osušeni,
usitnjeni i upotrebljeni za izradu vodenih disperzija u koncentracijama 2% i 4% na šejkeru LSB18
(Grant, Velika Britanija) tokom 24 h, na 37±1 °C i 100 o/min. Primenjena je metoda kontrolisane
brzine smicanja koja raste od 0 do 100 s-1, a zatim opada do 0 s-1 tokom 400 s na 37±0,1 °C na
reometru Rheolab MC120 (Paar Physica, Nemačka) sa mernim uređajem Z3 DIN. Posle 24 h
uzorci su bili potpuno hidratisani. Reogrami svih disperzija pokazuju proticanje sa tiksotropijom.
Najveće vrednosti tiksotropije određene su kod PEC pripremljenih pri pH 3,6, a najmanje pri
pH 4,6, nezavisno od korišćene kiseline i koncentracije PEC u disperziji. Struktuiranost uzoraka
procenjena je na osnovu vrednosti prividnog viskoziteta (ηmin na 100 s-1/ ηmax na 22,2 s-1).
Najveće vrednosti η pri koncentraciji 4% imali su uzorci pripremljeni sa SK pri pH 5,6 (1440/5450
mPa·s), a najmanje sa HK pri pH 4,6 (979/3440 mPa·s). Pri koncentraciji 2% najveće vrednosti
η imali su uzorci pripremljeni sa HK pri pH 3,6 (557/2010 mPa·s), a najmanje sa HK pri pH 4,6
(198/692 mPa·s). Može se zaključiti da su izbor kiseline i pH medijuma značajno uticali na jačinu
interakcija između polimera, i posledično na strukturu čvrstih PEC i reološke karakteristike
nakon hidratacije, što se može odraziti na kinetiku oslobađanja aktivnih supstanci.
AB  - Polyelectrolyte complexes (PECs) are formed by establishing ion interactions between
polymers at pH around their pKa. Formation and PEC rehydration capacity in physiological
fluids, which can affect the active substance release mechanism and rate, might depend on pH
and medium composition. The aim of this study is to examine the influence of pH of medium
and acid choice on rehydration of solid chitosan/xanthan PECs. Prepared chitosan/xanthan PEC
hydrogels at pH 3.6, 4.6 and 5.6 using hydrochloric (HA) and acetic (AA) acid were dried and
used for aqueous dispersions preparation at concentrations of 2% and 4% on LSB18 shaker
(Grant, UK) during 24 h, at 37±1 °C and 100 rpm. Controlled shear rate measurements were
performed on rheometer Rheolab MC120 (Paar Physica, Germany) with Z3 DIN measuring
device by increasing shear rate from 0 to 100 s-1 and back to 0 s-1, during 400 s at 37±0.1 °C.
Samples were completely hydrated after 24 h. All dispersions rheograms demonstrated flow
with thixotropy. The highest thixotropy values were determined for PECs prepared at pH 3.6,
and lowest at pH 4.6, independently of the used acid and PEC concentration. Sample structure
estimation was based on apparent viscosities (ηmin at 100 s-1/ηmax at 22.2 s-1). The highest η
at concentration of 4% had samples prepared with AA at pH 5.6 (1440/5450 mPa·s), and lowest
with HA at pH 4.6 (979/3440 mPa·s). At concentration of 2%, highest η had samples prepared
with HA at pH 3.6 (557/2010 mPa·s), and lowest with HA at pH 4.6 (198/692 mPa·s). It can be
concluded that acid choice and pH of medium significantly influenced the interaction intensity
between polymers, and consequently, solid PECs structure and rheological characteristics
after hydration, which can be reflected in active substance release kinetics.
PB  - Farmaceutska komora Crne Gore
PB  - Univerzitet Crne Gore, Medicinski fakultet, studijski program-farmacija
C3  - Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 2019. Budva, Bečići, Crna Gora, Zbornik sažetaka
T1  - Razvoj nosača lekovitih supstanci tipa polielektrolitnih kompleksa hitozan/ksantan: karakterizacija procesa rehidratacije in vitro
T1  - Development of drug delivery systems based on chitosan/xanthan polyelectrolyte complexes: in vitro characterization of rehydration process
SP  - 224
EP  - 225
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5368
ER  - 

@conference{
author = "Ćirić, Ana and Đekić, Ljiljana",
year = "2019",
abstract = "Polielektrolitni kompleksi (PEC) nastaju uspostavljanjem jonskih interakcija između polimera
pri pH oko njihovih pKa. Formiranje i kapacitet PEC za rehidrataciju u fiziološkim tečnostima,
koje može uticati na mehanizam i brzinu oslobađanja aktivne supstance, može zavisiti od
pH i prirode medijuma. Cilj rada je ispitivanje uticaja pH medijuma i upotrebljene kiseline na
rehidrataciju čvrstih PEC hitozana i ksantana. Pripremljeni hidrogelovi tipa PEC ksantana i
hitozana pri pH 3,6; 4,6 i 5,6, upotrebom hlorovodonične (HK) i sirćetne (SK) kiseline su osušeni,
usitnjeni i upotrebljeni za izradu vodenih disperzija u koncentracijama 2% i 4% na šejkeru LSB18
(Grant, Velika Britanija) tokom 24 h, na 37±1 °C i 100 o/min. Primenjena je metoda kontrolisane
brzine smicanja koja raste od 0 do 100 s-1, a zatim opada do 0 s-1 tokom 400 s na 37±0,1 °C na
reometru Rheolab MC120 (Paar Physica, Nemačka) sa mernim uređajem Z3 DIN. Posle 24 h
uzorci su bili potpuno hidratisani. Reogrami svih disperzija pokazuju proticanje sa tiksotropijom.
Najveće vrednosti tiksotropije određene su kod PEC pripremljenih pri pH 3,6, a najmanje pri
pH 4,6, nezavisno od korišćene kiseline i koncentracije PEC u disperziji. Struktuiranost uzoraka
procenjena je na osnovu vrednosti prividnog viskoziteta (ηmin na 100 s-1/ ηmax na 22,2 s-1).
Najveće vrednosti η pri koncentraciji 4% imali su uzorci pripremljeni sa SK pri pH 5,6 (1440/5450
mPa·s), a najmanje sa HK pri pH 4,6 (979/3440 mPa·s). Pri koncentraciji 2% najveće vrednosti
η imali su uzorci pripremljeni sa HK pri pH 3,6 (557/2010 mPa·s), a najmanje sa HK pri pH 4,6
(198/692 mPa·s). Može se zaključiti da su izbor kiseline i pH medijuma značajno uticali na jačinu
interakcija između polimera, i posledično na strukturu čvrstih PEC i reološke karakteristike
nakon hidratacije, što se može odraziti na kinetiku oslobađanja aktivnih supstanci., Polyelectrolyte complexes (PECs) are formed by establishing ion interactions between
polymers at pH around their pKa. Formation and PEC rehydration capacity in physiological
fluids, which can affect the active substance release mechanism and rate, might depend on pH
and medium composition. The aim of this study is to examine the influence of pH of medium
and acid choice on rehydration of solid chitosan/xanthan PECs. Prepared chitosan/xanthan PEC
hydrogels at pH 3.6, 4.6 and 5.6 using hydrochloric (HA) and acetic (AA) acid were dried and
used for aqueous dispersions preparation at concentrations of 2% and 4% on LSB18 shaker
(Grant, UK) during 24 h, at 37±1 °C and 100 rpm. Controlled shear rate measurements were
performed on rheometer Rheolab MC120 (Paar Physica, Germany) with Z3 DIN measuring
device by increasing shear rate from 0 to 100 s-1 and back to 0 s-1, during 400 s at 37±0.1 °C.
Samples were completely hydrated after 24 h. All dispersions rheograms demonstrated flow
with thixotropy. The highest thixotropy values were determined for PECs prepared at pH 3.6,
and lowest at pH 4.6, independently of the used acid and PEC concentration. Sample structure
estimation was based on apparent viscosities (ηmin at 100 s-1/ηmax at 22.2 s-1). The highest η
at concentration of 4% had samples prepared with AA at pH 5.6 (1440/5450 mPa·s), and lowest
with HA at pH 4.6 (979/3440 mPa·s). At concentration of 2%, highest η had samples prepared
with HA at pH 3.6 (557/2010 mPa·s), and lowest with HA at pH 4.6 (198/692 mPa·s). It can be
concluded that acid choice and pH of medium significantly influenced the interaction intensity
between polymers, and consequently, solid PECs structure and rheological characteristics
after hydration, which can be reflected in active substance release kinetics.",
publisher = "Farmaceutska komora Crne Gore, Univerzitet Crne Gore, Medicinski fakultet, studijski program-farmacija",
journal = "Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 2019. Budva, Bečići, Crna Gora, Zbornik sažetaka",
title = "Razvoj nosača lekovitih supstanci tipa polielektrolitnih kompleksa hitozan/ksantan: karakterizacija procesa rehidratacije in vitro, Development of drug delivery systems based on chitosan/xanthan polyelectrolyte complexes: in vitro characterization of rehydration process",
pages = "224-225",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5368"
}

Ćirić, A.,& Đekić, L.. (2019). Razvoj nosača lekovitih supstanci tipa polielektrolitnih kompleksa hitozan/ksantan: karakterizacija procesa rehidratacije in vitro. in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 2019. Budva, Bečići, Crna Gora, Zbornik sažetaka
Farmaceutska komora Crne Gore., 224-225.
https://hdl.handle.net/21.15107/rcub_farfar_5368

Ćirić A, Đekić L. Razvoj nosača lekovitih supstanci tipa polielektrolitnih kompleksa hitozan/ksantan: karakterizacija procesa rehidratacije in vitro. in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 2019. Budva, Bečići, Crna Gora, Zbornik sažetaka. 2019;:224-225.
https://hdl.handle.net/21.15107/rcub_farfar_5368 .

Ćirić, Ana, Đekić, Ljiljana, "Razvoj nosača lekovitih supstanci tipa polielektrolitnih kompleksa hitozan/ksantan: karakterizacija procesa rehidratacije in vitro" in Treći kongres farmaceuta Crne Gore sa međunarodnim učešćem, 2019. Budva, Bečići, Crna Gora, Zbornik sažetaka (2019):224-225,
https://hdl.handle.net/21.15107/rcub_farfar_5368 .

TY  - CONF
AU  - Ćirić, Ana
AU  - Mitrić, Miodrag
AU  - Dobričić, Vladimir
AU  - Đekić, Ljiljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5366
AB  - Polyelectrolyte complexes are novel drug delivery systems obtained by establishing ion interactions between two oppositely charged polymers. ...
PB  - University of Novi Sad, Faculty of Technology Novi Sad
C3  - 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)
T1  - Influence of drying method on chitosan/xanthan polyelectrolyte complex characteristics
SP  - 185
EP  - 185
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5366
ER  - 

@conference{
author = "Ćirić, Ana and Mitrić, Miodrag and Dobričić, Vladimir and Đekić, Ljiljana",
year = "2019",
abstract = "Polyelectrolyte complexes are novel drug delivery systems obtained by establishing ion interactions between two oppositely charged polymers. ...",
publisher = "University of Novi Sad, Faculty of Technology Novi Sad",
journal = "1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)",
title = "Influence of drying method on chitosan/xanthan polyelectrolyte complex characteristics",
pages = "185-185",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5366"
}

Ćirić, A., Mitrić, M., Dobričić, V.,& Đekić, L.. (2019). Influence of drying method on chitosan/xanthan polyelectrolyte complex characteristics. in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)
University of Novi Sad, Faculty of Technology Novi Sad., 185-185.
https://hdl.handle.net/21.15107/rcub_farfar_5366

Ćirić A, Mitrić M, Dobričić V, Đekić L. Influence of drying method on chitosan/xanthan polyelectrolyte complex characteristics. in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts). 2019;:185-185.
https://hdl.handle.net/21.15107/rcub_farfar_5366 .

Ćirić, Ana, Mitrić, Miodrag, Dobričić, Vladimir, Đekić, Ljiljana, "Influence of drying method on chitosan/xanthan polyelectrolyte complex characteristics" in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts) (2019):185-185,
https://hdl.handle.net/21.15107/rcub_farfar_5366 .

TY  - CONF
AU  - Ćirić, Ana
AU  - Đekić, Ljiljana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5367
AB  - Ibuprofen is one of the most frequently used analgesic with good risk/benefit ratio. Due to its short half-life (t1/2 ~ 2 h), frequent administration of immediate release dosage forms is necessary. ...
PB  - University of Novi Sad, Faculty of Technology Novi Sad
C3  - 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)
T1  - In vitro characterization of rehydration process and dissolution of ibuprofen from chitosan/xanthan polyelectrolyte complex based drug delivery systems
SP  - 186
EP  - 186
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5367
ER  - 

@conference{
author = "Ćirić, Ana and Đekić, Ljiljana",
year = "2019",
abstract = "Ibuprofen is one of the most frequently used analgesic with good risk/benefit ratio. Due to its short half-life (t1/2 ~ 2 h), frequent administration of immediate release dosage forms is necessary. ...",
publisher = "University of Novi Sad, Faculty of Technology Novi Sad",
journal = "1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)",
title = "In vitro characterization of rehydration process and dissolution of ibuprofen from chitosan/xanthan polyelectrolyte complex based drug delivery systems",
pages = "186-186",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5367"
}

Ćirić, A.,& Đekić, L.. (2019). In vitro characterization of rehydration process and dissolution of ibuprofen from chitosan/xanthan polyelectrolyte complex based drug delivery systems. in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts)
University of Novi Sad, Faculty of Technology Novi Sad., 186-186.
https://hdl.handle.net/21.15107/rcub_farfar_5367

Ćirić A, Đekić L. In vitro characterization of rehydration process and dissolution of ibuprofen from chitosan/xanthan polyelectrolyte complex based drug delivery systems. in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts). 2019;:186-186.
https://hdl.handle.net/21.15107/rcub_farfar_5367 .

Ćirić, Ana, Đekić, Ljiljana, "In vitro characterization of rehydration process and dissolution of ibuprofen from chitosan/xanthan polyelectrolyte complex based drug delivery systems" in 1st International Conference on Advanced Production and Processing 10th-11th October 2019 Novi Sad, Serbia (Book of Abstracts) (2019):186-186,
https://hdl.handle.net/21.15107/rcub_farfar_5367 .

TY  - THES
AU  - Lavrič, Olivera Lj.
PY  - 2019
UR  - http://nardus.mpn.gov.rs/handle/123456789/12128
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7285
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:21046/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=2048410466
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3694
AB  - Cilj ovog istraživanja bio je razvoj tableta sa pulsnim oslobađanjem karvedilola,pogodnih za korišćenje u hronoterapiji, korišćenjem tehnika elektropredenja i oblaganjakompresijom. Istraživanje se sastojalo iz četiri dela.U prvom delu istraživanja vršeno je ispitivanje stepena mešanja karvedilola i Soluplus®polimera korišćenjem dve metode. Najpre, određivanjem razlike ukupnih parametararastvorljivosti ove dve komponente, a potom i određivanjem Flory-Hugginsinterakcionog parametra. Parcijalni i ukupni parametar rastvorljivosti karvediloladobijeni su Stefanis-Panayiotou metodom, a potom je određena razlika ukupnogparametra rastvorljivosti karvedilola i polimera. Izračunata vrednost iznosila je 5,1MPa1/2, i ukazala je da u sistemu ove dve komponente najverovatnije dolazi do mešanja.Rezultati druge metode, tj. određena vrednost interakcionog parametra, koja je iznosila -2,3054; ukazala je na veliku verovatnoću da se karvedilol i Soluplus® mešaju.U drugoj fazi eksperimentalnog istraživanja vršen je razvoj formulacije nanovlakanaSoluplus®-a tehnikom elektropredenja. Određen je region rastvorljivosti za polimerSoluplus® na ternernom grafiku, koristeći frakcione parametre rastvorljivosti odabranihrastvarača. Potom su rastvarači iz definisanog regiona rastvorljivosti kategorisani naosnovu njihove dielektrične konstante, kao i sa aspekta mogućnosti rastvaranjakarvedilola, u cilju procene njihove pogodnosti za proces elektropredenja. Upreliminarnoj fazi, izvršeno je elektropredenje Soluplus®-a u različitim rastvaračima, gdeje na osnovu posmatranja morfologije dobijenih vlakana pod optičkim mikroskopom, kaoi na osnovu stabilnosti procesa (pojavom Taylor-ove kupe), definisan optimalan rastvaračza dobijanje nanovlakana Soluplus®-a impregniranih karvedilolom. Definisane suformulacije sa različitim udelom karvedilola (5-50% m/m u odnosu na suvu masuvlakana) u 20% rastvoru Soluplus®-a, u smeši rastvarača aceton-hloroform (90:10(m/m)), i izvršena je karakterizacija dobijenih nanovlakana. Rezultati su pokazali da jeprocenat inkorporiranog karvedilola u vlaknima bio od 84 do 93%. Skenirajućaelektronska mikroskopija je pokazala da su dobijena vlakna uniformne, glatke strukture,pri čemu se sa povećanjem udela karvedilola smanjuje broj proširenja na vlaknima.Pokazano je da nema kristala karvedilola na površini vlakana, čime je pretpostavljeno daje inkorporiran u vlakna, a diferencijalna skenirajuća kalorimetrija je ukazala na odsustvokristalnog oblika karvedilola u svim formulacijama. Infracrvena spektroskopija saFurijeovom transformacijom je pokazala odsustvo karakterističnih pikova karvedilola unanovaknima. Brzina rastvaranja karvedilola iz nanovlakana bila je veća u odnosu nakristalni oblik čiste supstance (karvedilola).U trećoj fazi eksperimentalnog istraživanja cilj je bio razvoj formulacija tableta satrenutnim oslobađanjem karvedilola koršćenjem direktne kompresije. Ispitivano jepostojanje razlike u brzini rastvaranja karvedilola između tableta koje su sadržalekonvencionalne ekscipijense i tableta dobijenih kompresijom nanovlakana Soluplus®-aimpregniranih karvedilolom. Brzina rastvaranja karvedilola se značajno razlikovala samou prvih 15 minuta...
AB  - The aim of this work was the development of tablets with pulse release profile ofcarvedilol, suitable for chronotherapy. Electrospinning and compression coating wereused in the preparation of tablets. The research activities were divided in four parts.In the first part, the degree of miscibility of carvedilol with polymers was studied usingtwo methods. Using the first method, the difference of total solubility parameters of thetwo components of mixture was determined, while for the second method, the calculationof Flory-Huggins interaction parameter was made. Partial and total solubility parametersof carvedilol were calculated according to the method developed by Stefanis-Panayiotouwhich was followed by calculating the difference of total solubility parameters ofcarvedilol and polymer. The calculated value was 5.1MPa1/2 suggesting that mixing ofthe two components would most likely occur. The determination of Flory-Hugginsinteraction parameter resulted in the value of interaction parameter of -2.3054, implying,with high likelihood, that carvedilol and Soluplus® would form a mixture.In the second part of research activities Soluplus® nanofibers were developed usingelectrospinning technique. The solubility region of Soluplus® polymer in selectedsolvents was determined by using ternary diagram constructed by employing fractionalsolubility parameters. Solvents from the defined solubility region were then categorizedaccording to their dielectric constants as well as their ability to dissolve carvedilol in orderto evaluate their suitability for the electrospinning process. In the preliminary steps,Soluplus® was dissolved in different selected solvents and then electrospinned. Processstability, assessed by observing the occurrence (or absence) of Taylor cone, and theresulting fiber morphology, assessed by optical microscopy, were used to define theoptimal solvent for Soluplus® nanofibers with impregnated carvedilol. 20% solutions ofSoluplus® in a mixture of acetone-chlorophorm (90:10 (m/m)) with added carvedilol (5-50% of total dry mass) were electrosprayed and the resulting nanofibers subsequentlycharacterized. Encapsulation efficiency of carvedilol in Soluplus® nanofibers was foundto be 84% to 93%. Scanning electron microscopy of electrospun samples revealeduniform nanofibers with smooth surfaces, where increasing mass percentage of carvediloldecreased the number and occurrence of beads. Absence of crystalline particles ofcarvedilol on the surface of nanofibers implied full incorporation into nanofibers whilethe results of differential scanning calorimetry revealed the absence of crystallinecarvedilol for all formulation. Spectra of nanofibers measured by infrared spectroscopy(with fast Fourirer transform) revealed absence of characteristic peaks of carvedilol.Dissolution rate Soluplus® nanofibers with carvedilol was higher relative to thecrystalline form of pure carvedilol.In the third part, the goal was the development of tablet formulation with instant releaseof carvedilol prepared by direct compression. Dissolution rates of carvedilol from tabletsprepared from conventional excipients were compared to those determined for tabletsprepared by compressing Soluplus® nanofibers with carvedilol.
PB  - Универзитет у Београду, Фармацеутски факултет
T2  - Универзитет у Београду
T1  - Farmaceutski razvoj tableta sa pulsnim oslobađanjem karvedilola tehnikama elektropredenja i oblaganja kompresijom
UR  - https://hdl.handle.net/21.15107/rcub_nardus_12128
ER  - 

@phdthesis{
author = "Lavrič, Olivera Lj.",
year = "2019",
abstract = "Cilj ovog istraživanja bio je razvoj tableta sa pulsnim oslobađanjem karvedilola,pogodnih za korišćenje u hronoterapiji, korišćenjem tehnika elektropredenja i oblaganjakompresijom. Istraživanje se sastojalo iz četiri dela.U prvom delu istraživanja vršeno je ispitivanje stepena mešanja karvedilola i Soluplus®polimera korišćenjem dve metode. Najpre, određivanjem razlike ukupnih parametararastvorljivosti ove dve komponente, a potom i određivanjem Flory-Hugginsinterakcionog parametra. Parcijalni i ukupni parametar rastvorljivosti karvediloladobijeni su Stefanis-Panayiotou metodom, a potom je određena razlika ukupnogparametra rastvorljivosti karvedilola i polimera. Izračunata vrednost iznosila je 5,1MPa1/2, i ukazala je da u sistemu ove dve komponente najverovatnije dolazi do mešanja.Rezultati druge metode, tj. određena vrednost interakcionog parametra, koja je iznosila -2,3054; ukazala je na veliku verovatnoću da se karvedilol i Soluplus® mešaju.U drugoj fazi eksperimentalnog istraživanja vršen je razvoj formulacije nanovlakanaSoluplus®-a tehnikom elektropredenja. Određen je region rastvorljivosti za polimerSoluplus® na ternernom grafiku, koristeći frakcione parametre rastvorljivosti odabranihrastvarača. Potom su rastvarači iz definisanog regiona rastvorljivosti kategorisani naosnovu njihove dielektrične konstante, kao i sa aspekta mogućnosti rastvaranjakarvedilola, u cilju procene njihove pogodnosti za proces elektropredenja. Upreliminarnoj fazi, izvršeno je elektropredenje Soluplus®-a u različitim rastvaračima, gdeje na osnovu posmatranja morfologije dobijenih vlakana pod optičkim mikroskopom, kaoi na osnovu stabilnosti procesa (pojavom Taylor-ove kupe), definisan optimalan rastvaračza dobijanje nanovlakana Soluplus®-a impregniranih karvedilolom. Definisane suformulacije sa različitim udelom karvedilola (5-50% m/m u odnosu na suvu masuvlakana) u 20% rastvoru Soluplus®-a, u smeši rastvarača aceton-hloroform (90:10(m/m)), i izvršena je karakterizacija dobijenih nanovlakana. Rezultati su pokazali da jeprocenat inkorporiranog karvedilola u vlaknima bio od 84 do 93%. Skenirajućaelektronska mikroskopija je pokazala da su dobijena vlakna uniformne, glatke strukture,pri čemu se sa povećanjem udela karvedilola smanjuje broj proširenja na vlaknima.Pokazano je da nema kristala karvedilola na površini vlakana, čime je pretpostavljeno daje inkorporiran u vlakna, a diferencijalna skenirajuća kalorimetrija je ukazala na odsustvokristalnog oblika karvedilola u svim formulacijama. Infracrvena spektroskopija saFurijeovom transformacijom je pokazala odsustvo karakterističnih pikova karvedilola unanovaknima. Brzina rastvaranja karvedilola iz nanovlakana bila je veća u odnosu nakristalni oblik čiste supstance (karvedilola).U trećoj fazi eksperimentalnog istraživanja cilj je bio razvoj formulacija tableta satrenutnim oslobađanjem karvedilola koršćenjem direktne kompresije. Ispitivano jepostojanje razlike u brzini rastvaranja karvedilola između tableta koje su sadržalekonvencionalne ekscipijense i tableta dobijenih kompresijom nanovlakana Soluplus®-aimpregniranih karvedilolom. Brzina rastvaranja karvedilola se značajno razlikovala samou prvih 15 minuta..., The aim of this work was the development of tablets with pulse release profile ofcarvedilol, suitable for chronotherapy. Electrospinning and compression coating wereused in the preparation of tablets. The research activities were divided in four parts.In the first part, the degree of miscibility of carvedilol with polymers was studied usingtwo methods. Using the first method, the difference of total solubility parameters of thetwo components of mixture was determined, while for the second method, the calculationof Flory-Huggins interaction parameter was made. Partial and total solubility parametersof carvedilol were calculated according to the method developed by Stefanis-Panayiotouwhich was followed by calculating the difference of total solubility parameters ofcarvedilol and polymer. The calculated value was 5.1MPa1/2 suggesting that mixing ofthe two components would most likely occur. The determination of Flory-Hugginsinteraction parameter resulted in the value of interaction parameter of -2.3054, implying,with high likelihood, that carvedilol and Soluplus® would form a mixture.In the second part of research activities Soluplus® nanofibers were developed usingelectrospinning technique. The solubility region of Soluplus® polymer in selectedsolvents was determined by using ternary diagram constructed by employing fractionalsolubility parameters. Solvents from the defined solubility region were then categorizedaccording to their dielectric constants as well as their ability to dissolve carvedilol in orderto evaluate their suitability for the electrospinning process. In the preliminary steps,Soluplus® was dissolved in different selected solvents and then electrospinned. Processstability, assessed by observing the occurrence (or absence) of Taylor cone, and theresulting fiber morphology, assessed by optical microscopy, were used to define theoptimal solvent for Soluplus® nanofibers with impregnated carvedilol. 20% solutions ofSoluplus® in a mixture of acetone-chlorophorm (90:10 (m/m)) with added carvedilol (5-50% of total dry mass) were electrosprayed and the resulting nanofibers subsequentlycharacterized. Encapsulation efficiency of carvedilol in Soluplus® nanofibers was foundto be 84% to 93%. Scanning electron microscopy of electrospun samples revealeduniform nanofibers with smooth surfaces, where increasing mass percentage of carvediloldecreased the number and occurrence of beads. Absence of crystalline particles ofcarvedilol on the surface of nanofibers implied full incorporation into nanofibers whilethe results of differential scanning calorimetry revealed the absence of crystallinecarvedilol for all formulation. Spectra of nanofibers measured by infrared spectroscopy(with fast Fourirer transform) revealed absence of characteristic peaks of carvedilol.Dissolution rate Soluplus® nanofibers with carvedilol was higher relative to thecrystalline form of pure carvedilol.In the third part, the goal was the development of tablet formulation with instant releaseof carvedilol prepared by direct compression. Dissolution rates of carvedilol from tabletsprepared from conventional excipients were compared to those determined for tabletsprepared by compressing Soluplus® nanofibers with carvedilol.",
publisher = "Универзитет у Београду, Фармацеутски факултет",
journal = "Универзитет у Београду",
title = "Farmaceutski razvoj tableta sa pulsnim oslobađanjem karvedilola tehnikama elektropredenja i oblaganja kompresijom",
url = "https://hdl.handle.net/21.15107/rcub_nardus_12128"
}

Lavrič, O. Lj.. (2019). Farmaceutski razvoj tableta sa pulsnim oslobađanjem karvedilola tehnikama elektropredenja i oblaganja kompresijom. in Универзитет у Београду
Универзитет у Београду, Фармацеутски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_12128

Lavrič OL. Farmaceutski razvoj tableta sa pulsnim oslobađanjem karvedilola tehnikama elektropredenja i oblaganja kompresijom. in Универзитет у Београду. 2019;.
https://hdl.handle.net/21.15107/rcub_nardus_12128 .

Lavrič, Olivera Lj., "Farmaceutski razvoj tableta sa pulsnim oslobađanjem karvedilola tehnikama elektropredenja i oblaganja kompresijom" in Универзитет у Београду (2019),
https://hdl.handle.net/21.15107/rcub_nardus_12128 .

TY  - JOUR
AU  - Madžarević, Marijana
AU  - Medarević, Đorđe
AU  - Vulović, Aleksandra
AU  - Šušteršič, Tijana
AU  - Đuriš, Jelena
AU  - Filipović, Nenad
AU  - Ibrić, Svetlana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3466
AB  - The aim of this work was to investigate eects of the formulation factors on tablet printability as well as to optimize and predict extended drug release from cross-linked polymeric ibuprofen printlets using an artificial neural network (ANN). Printlets were printed using digital light processing (DLP) technology from formulations containing polyethylene glycol diacrylate, polyethylene glycol, and water in concentrations according to D-optimal mixture design and 0.1% w/w riboflavin and 5% w/w ibuprofen. It was observed that with higher water content longer exposure time was required for successful printing. For understanding the eects of excipients and printing parameters on drug dissolution rate in DLP printlets two dierent neural networks were developed with using two commercially available softwares. After comparison of experimental and predicted values of in vitro dissolution at the corresponding time points for optimized formulation, the R2 experimental vs. predicted value was 0.9811 (neural network 1) and 0.9960 (neural network 2). According to dierence f1 and similarity factor f2 (f1 = 14.30 and f2 = 52.15) neural network 1 with supervised multilayer perceptron, backpropagation algorithm, and linear activation function gave a similar dissolution profile to obtained experimental results, indicating that adequate ANN is able to set out an input–output relationship in DLP printing of pharmaceutics.
PB  - MDPI
T2  - Pharmaceutics
T1  - Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks
VL  - 11
IS  - 10
SP  - 1
EP  - 16
DO  - 10.3390/pharmaceutics11100544
ER  - 

@article{
author = "Madžarević, Marijana and Medarević, Đorđe and Vulović, Aleksandra and Šušteršič, Tijana and Đuriš, Jelena and Filipović, Nenad and Ibrić, Svetlana",
year = "2019",
abstract = "The aim of this work was to investigate eects of the formulation factors on tablet printability as well as to optimize and predict extended drug release from cross-linked polymeric ibuprofen printlets using an artificial neural network (ANN). Printlets were printed using digital light processing (DLP) technology from formulations containing polyethylene glycol diacrylate, polyethylene glycol, and water in concentrations according to D-optimal mixture design and 0.1% w/w riboflavin and 5% w/w ibuprofen. It was observed that with higher water content longer exposure time was required for successful printing. For understanding the eects of excipients and printing parameters on drug dissolution rate in DLP printlets two dierent neural networks were developed with using two commercially available softwares. After comparison of experimental and predicted values of in vitro dissolution at the corresponding time points for optimized formulation, the R2 experimental vs. predicted value was 0.9811 (neural network 1) and 0.9960 (neural network 2). According to dierence f1 and similarity factor f2 (f1 = 14.30 and f2 = 52.15) neural network 1 with supervised multilayer perceptron, backpropagation algorithm, and linear activation function gave a similar dissolution profile to obtained experimental results, indicating that adequate ANN is able to set out an input–output relationship in DLP printing of pharmaceutics.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks",
volume = "11",
number = "10",
pages = "1-16",
doi = "10.3390/pharmaceutics11100544"
}

Madžarević, M., Medarević, Đ., Vulović, A., Šušteršič, T., Đuriš, J., Filipović, N.,& Ibrić, S.. (2019). Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks. in Pharmaceutics
MDPI., 11(10), 1-16.
https://doi.org/10.3390/pharmaceutics11100544

Madžarević M, Medarević Đ, Vulović A, Šušteršič T, Đuriš J, Filipović N, Ibrić S. Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks. in Pharmaceutics. 2019;11(10):1-16.
doi:10.3390/pharmaceutics11100544 .

Madžarević, Marijana, Medarević, Đorđe, Vulović, Aleksandra, Šušteršič, Tijana, Đuriš, Jelena, Filipović, Nenad, Ibrić, Svetlana, "Optimization and prediction of ibuprofen release from 3D DLP printlets using artificial neural networks" in Pharmaceutics, 11, no. 10 (2019):1-16,
https://doi.org/10.3390/pharmaceutics11100544 . .

TY  - JOUR
AU  - Krkobabić, Mirjana
AU  - Medarević, Đorđe
AU  - Cvijić, Sandra
AU  - Grujić, Branka
AU  - Ibrić, Svetlana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3540
AB  - Three-dimensional (3D) printing enables the production of different objects adjusted for the specific application, which has particular importance of providing personalized therapy, whereby the challenge is to apply pharmaceutical materials into 3D printing technology. In this study, effect of poly(ethylene glycol) 400 (PEG 400), sodium chloride (NaCl), and mannitol, as hydrophilic excipients, was investigated in order to overcome very slow and incomplete drug release from tablets (printlets) fabricated by photopolymerization using digital light processing (DLP) technology. Paracetamol (acetaminophen) was used as a model drug, while polyethylene glycol diacrylate (PEGDA) was used as a photopolymer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide as a photoinitiator in photoreactive mixtures. Most of printlet formulations exhibit sustained release over 8 h, wherein drug release kinetics is the best described with Korsmeyer-Peppas kinetics. Variation in the content of photopolymer and excipients had an influence on the dissolution rate, mechanical characteristics, and internal structure of the investigated samples. The addition of hydrophilic polymers increased drug release rate, while PEGDA had the greatest influence on the tensile strength of printlets. The results indicate the possibility of implementation of traditional excipients into different formulations for photopolymerization based 3D printing for the production of small batches of tablets with tailored drug release.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate
VL  - 572
DO  - 10.1016/j.ijpharm.2019.118790
ER  - 

@article{
author = "Krkobabić, Mirjana and Medarević, Đorđe and Cvijić, Sandra and Grujić, Branka and Ibrić, Svetlana",
year = "2019",
abstract = "Three-dimensional (3D) printing enables the production of different objects adjusted for the specific application, which has particular importance of providing personalized therapy, whereby the challenge is to apply pharmaceutical materials into 3D printing technology. In this study, effect of poly(ethylene glycol) 400 (PEG 400), sodium chloride (NaCl), and mannitol, as hydrophilic excipients, was investigated in order to overcome very slow and incomplete drug release from tablets (printlets) fabricated by photopolymerization using digital light processing (DLP) technology. Paracetamol (acetaminophen) was used as a model drug, while polyethylene glycol diacrylate (PEGDA) was used as a photopolymer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide as a photoinitiator in photoreactive mixtures. Most of printlet formulations exhibit sustained release over 8 h, wherein drug release kinetics is the best described with Korsmeyer-Peppas kinetics. Variation in the content of photopolymer and excipients had an influence on the dissolution rate, mechanical characteristics, and internal structure of the investigated samples. The addition of hydrophilic polymers increased drug release rate, while PEGDA had the greatest influence on the tensile strength of printlets. The results indicate the possibility of implementation of traditional excipients into different formulations for photopolymerization based 3D printing for the production of small batches of tablets with tailored drug release.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate",
volume = "572",
doi = "10.1016/j.ijpharm.2019.118790"
}

Krkobabić, M., Medarević, Đ., Cvijić, S., Grujić, B.,& Ibrić, S.. (2019). Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate. in International Journal of Pharmaceutics
Elsevier., 572.
https://doi.org/10.1016/j.ijpharm.2019.118790

Krkobabić M, Medarević Đ, Cvijić S, Grujić B, Ibrić S. Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate. in International Journal of Pharmaceutics. 2019;572.
doi:10.1016/j.ijpharm.2019.118790 .

Krkobabić, Mirjana, Medarević, Đorđe, Cvijić, Sandra, Grujić, Branka, Ibrić, Svetlana, "Hydrophilic excipients in digital light processing (DLP) printing of sustained release tablets: Impact on internal structure and drug dissolution rate" in International Journal of Pharmaceutics, 572 (2019),
https://doi.org/10.1016/j.ijpharm.2019.118790 . .

TY  - JOUR
AU  - Ćetković, Zora
AU  - Cvijić, Sandra
AU  - Vasiljević, Dragana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3457
AB  - Formulation of lipid-based drug delivery systems is recognized as a promising strategy to increase bioavailability of simvastatin (SV). The purpose of this study was to formulate advantageous lipid-based drug delivery systems for pH-controlled release of SV using polymethacrylate polymers (Eudragit®) as carriers. Liquid SV-loaded self-microemulsifying drug delivery systems (SMEDDS), composed of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, or propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (PEG-15 hydroxystearate), were characterized in terms of emulsification time, robustness to dilution, and droplet size. To enable targeted SV release at desired pH, the liquid SMEDDS were mixed with solid carriers, Eudragit® L100 and/or Eudragit® S100. The resulting gel-like lipid-based drug delivery systems were transparent and ductile, and exhibited viscoelastic rheological properties. In vitro dissolution data indicated sustained SV release in pH medium corresponding to distal ileum. The simulation results revealed that sustained SV release from the designed systems is expected to increase SV bioavailability. Overall, our results demonstrate that sustained-release drug delivery systems, composed of liquid SMEDDS and polymethacrylate carriers (Eudragit® polymers), have the potential to enhance oral bioavailability of drugs with preferred absorption site in the pH medium corresponding to distal ileum.
PB  - Elsevier
T2  - Journal of Drug Delivery Science and Technology
T1  - Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin
VL  - 53
SP  - 1
EP  - 9
DO  - 10.1016/j.jddst.2019.101222
ER  - 

@article{
author = "Ćetković, Zora and Cvijić, Sandra and Vasiljević, Dragana",
year = "2019",
abstract = "Formulation of lipid-based drug delivery systems is recognized as a promising strategy to increase bioavailability of simvastatin (SV). The purpose of this study was to formulate advantageous lipid-based drug delivery systems for pH-controlled release of SV using polymethacrylate polymers (Eudragit®) as carriers. Liquid SV-loaded self-microemulsifying drug delivery systems (SMEDDS), composed of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, or propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (PEG-15 hydroxystearate), were characterized in terms of emulsification time, robustness to dilution, and droplet size. To enable targeted SV release at desired pH, the liquid SMEDDS were mixed with solid carriers, Eudragit® L100 and/or Eudragit® S100. The resulting gel-like lipid-based drug delivery systems were transparent and ductile, and exhibited viscoelastic rheological properties. In vitro dissolution data indicated sustained SV release in pH medium corresponding to distal ileum. The simulation results revealed that sustained SV release from the designed systems is expected to increase SV bioavailability. Overall, our results demonstrate that sustained-release drug delivery systems, composed of liquid SMEDDS and polymethacrylate carriers (Eudragit® polymers), have the potential to enhance oral bioavailability of drugs with preferred absorption site in the pH medium corresponding to distal ileum.",
publisher = "Elsevier",
journal = "Journal of Drug Delivery Science and Technology",
title = "Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin",
volume = "53",
pages = "1-9",
doi = "10.1016/j.jddst.2019.101222"
}

Ćetković, Z., Cvijić, S.,& Vasiljević, D.. (2019). Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin. in Journal of Drug Delivery Science and Technology
Elsevier., 53, 1-9.
https://doi.org/10.1016/j.jddst.2019.101222

Ćetković Z, Cvijić S, Vasiljević D. Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin. in Journal of Drug Delivery Science and Technology. 2019;53:1-9.
doi:10.1016/j.jddst.2019.101222 .

Ćetković, Zora, Cvijić, Sandra, Vasiljević, Dragana, "Formulation and characterization of novel lipid-based drug delivery systems containing polymethacrylate polymers as solid carriers for sustained release of simvastatin" in Journal of Drug Delivery Science and Technology, 53 (2019):1-9,
https://doi.org/10.1016/j.jddst.2019.101222 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Milovanović, Stoja
AU  - Medarević, Đorđe
AU  - Dobričić, Vladimir
AU  - Dapcević, Aleksandra
AU  - Ibrić, Svetlana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3324
AB  - Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO2 assisted method, solid dispersions of CARV with the selected (co) polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus (R) and Eudragit (R)) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated delta(p) values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions
VL  - 554
SP  - 190
EP  - 200
DO  - 10.1016/j.ijpharm.2018.11.015
ER  - 

@article{
author = "Đuriš, Jelena and Milovanović, Stoja and Medarević, Đorđe and Dobričić, Vladimir and Dapcević, Aleksandra and Ibrić, Svetlana",
year = "2019",
abstract = "Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO2 assisted method, solid dispersions of CARV with the selected (co) polymers (polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC), Soluplus (R) and Eudragit (R)) were obtained. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated delta(p) values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions",
volume = "554",
pages = "190-200",
doi = "10.1016/j.ijpharm.2018.11.015"
}

Đuriš, J., Milovanović, S., Medarević, Đ., Dobričić, V., Dapcević, A.,& Ibrić, S.. (2019). Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 554, 190-200.
https://doi.org/10.1016/j.ijpharm.2018.11.015

Đuriš J, Milovanović S, Medarević Đ, Dobričić V, Dapcević A, Ibrić S. Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions. in International Journal of Pharmaceutics. 2019;554:190-200.
doi:10.1016/j.ijpharm.2018.11.015 .

Đuriš, Jelena, Milovanović, Stoja, Medarević, Đorđe, Dobričić, Vladimir, Dapcević, Aleksandra, Ibrić, Svetlana, "Selection of the suitable polymer for supercritical fluid assisted preparation of carvedilol solid dispersions" in International Journal of Pharmaceutics, 554 (2019):190-200,
https://doi.org/10.1016/j.ijpharm.2018.11.015 . .

TY  - JOUR
AU  - Milovanović, S
AU  - Đuriš, Jelena
AU  - Dapcević, Aleksandra
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Zizović, I
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3252
AB  - The present work is aimed towards designing advanced materials by means of sustainable processes. In that sense, the utilization of supercritical CO 2 (scCO 2 ) for processing of pharmaceutical polymers (Soluplus ® , Eudragit ® , and hydroxypropyl methylcellulose acetate succinate), alone and with an addition of cardiovascular drug Carvedilol, was explored. Employed single-step static scCO 2 process (pressure of 30 MPa and temperature of 100 °C for 2 h) enabled fabrication of solvent-free polymeric foams and Carvedilol solid dispersions with controlled microstructure and average pore diameter of 101–257 μm suitable for application in the pharmaceutical industry. ScCO 2 did not remain in the foams after processing or affected the polymer composition, while Carvedilol formed hydrogen bonds with the polymers. Carvedilol was molecularly dispersed in the fabricated solid dispersions and its transition from the crystalline to amorphous form was complete. Korsmeyer-Peppas model was successfully used for the mathematical description of Carvedilol dissolution from solid dispersions. The dissolution rate of Carvedilol in acidic medium was significantly enhanced by its dispersion in tested polymers using the proposed high-pressure method.
PB  - Elsevier Ltd
T2  - Polymer Testing
T1  - Soluplus ® , Eudragit ® , HPMC-AS foams and solid dispersions for enhancement of Carvedilol dissolution rate prepared by a supercritical CO 2 process
VL  - 76
SP  - 54
EP  - 64
DO  - 10.1016/j.polymertesting.2019.03.001
ER  - 

@article{
author = "Milovanović, S and Đuriš, Jelena and Dapcević, Aleksandra and Medarević, Đorđe and Ibrić, Svetlana and Zizović, I",
year = "2019",
abstract = "The present work is aimed towards designing advanced materials by means of sustainable processes. In that sense, the utilization of supercritical CO 2 (scCO 2 ) for processing of pharmaceutical polymers (Soluplus ® , Eudragit ® , and hydroxypropyl methylcellulose acetate succinate), alone and with an addition of cardiovascular drug Carvedilol, was explored. Employed single-step static scCO 2 process (pressure of 30 MPa and temperature of 100 °C for 2 h) enabled fabrication of solvent-free polymeric foams and Carvedilol solid dispersions with controlled microstructure and average pore diameter of 101–257 μm suitable for application in the pharmaceutical industry. ScCO 2 did not remain in the foams after processing or affected the polymer composition, while Carvedilol formed hydrogen bonds with the polymers. Carvedilol was molecularly dispersed in the fabricated solid dispersions and its transition from the crystalline to amorphous form was complete. Korsmeyer-Peppas model was successfully used for the mathematical description of Carvedilol dissolution from solid dispersions. The dissolution rate of Carvedilol in acidic medium was significantly enhanced by its dispersion in tested polymers using the proposed high-pressure method.",
publisher = "Elsevier Ltd",
journal = "Polymer Testing",
title = "Soluplus ® , Eudragit ® , HPMC-AS foams and solid dispersions for enhancement of Carvedilol dissolution rate prepared by a supercritical CO 2 process",
volume = "76",
pages = "54-64",
doi = "10.1016/j.polymertesting.2019.03.001"
}

Milovanović, S., Đuriš, J., Dapcević, A., Medarević, Đ., Ibrić, S.,& Zizović, I.. (2019). Soluplus ® , Eudragit ® , HPMC-AS foams and solid dispersions for enhancement of Carvedilol dissolution rate prepared by a supercritical CO 2 process. in Polymer Testing
Elsevier Ltd., 76, 54-64.
https://doi.org/10.1016/j.polymertesting.2019.03.001

Milovanović S, Đuriš J, Dapcević A, Medarević Đ, Ibrić S, Zizović I. Soluplus ® , Eudragit ® , HPMC-AS foams and solid dispersions for enhancement of Carvedilol dissolution rate prepared by a supercritical CO 2 process. in Polymer Testing. 2019;76:54-64.
doi:10.1016/j.polymertesting.2019.03.001 .

Milovanović, S, Đuriš, Jelena, Dapcević, Aleksandra, Medarević, Đorđe, Ibrić, Svetlana, Zizović, I, "Soluplus ® , Eudragit ® , HPMC-AS foams and solid dispersions for enhancement of Carvedilol dissolution rate prepared by a supercritical CO 2 process" in Polymer Testing, 76 (2019):54-64,
https://doi.org/10.1016/j.polymertesting.2019.03.001 . .

TY  - JOUR
AU  - Gatarić, Biljana
AU  - Parojčić, Jelena
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3294
AB  - Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (P-eff). The P-eff values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of P-eff over D/S. Two P-eff cut-off values (1 x 10(-4) and 2.7 x 10(-4) cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.
PB  - Wiley, Hoboken
T2  - Biopharmaceutics & Drug Disposition
T1  - Application of data mining approach to identify drug subclasses based on solubility and permeability
VL  - 40
IS  - 2
SP  - 51
EP  - 61
DO  - 10.1002/bdd.2170
ER  - 

@article{
author = "Gatarić, Biljana and Parojčić, Jelena",
year = "2019",
abstract = "Solubility and permeability are recognized as key parameters governing drug intestinal absorption and represent the basis for biopharmaceutics drug classification. The Biopharmaceutics Classification System (BCS) is widely accepted and adopted by regulatory agencies. However, currently established low/high permeability and solubility boundaries are the subject of the ongoing scientific discussion. The aim of the present study was to apply data mining analysis on the selected drugs data set in order to develop a human permeability predictive model based on selected molecular descriptors, and to perform data clustering and classification to identify drug subclasses with respect to dose/solubility ratio (D/S) and effective permeability (P-eff). The P-eff values predicted for 30 model drugs for which experimental human permeability data are not available were in good agreement with the reported fraction of drug absorbed. The results of clustering and classification analysis indicate the predominant influence of P-eff over D/S. Two P-eff cut-off values (1 x 10(-4) and 2.7 x 10(-4) cm/s) have been identified indicating the existence of an intermediate group of drugs with moderate permeability. Advanced computational analysis employed in the present study enabled the recognition of complex relationships and patterns within physicochemical and biopharmaceutical properties associated with drug bioperformance.",
publisher = "Wiley, Hoboken",
journal = "Biopharmaceutics & Drug Disposition",
title = "Application of data mining approach to identify drug subclasses based on solubility and permeability",
volume = "40",
number = "2",
pages = "51-61",
doi = "10.1002/bdd.2170"
}

Gatarić, B.,& Parojčić, J.. (2019). Application of data mining approach to identify drug subclasses based on solubility and permeability. in Biopharmaceutics & Drug Disposition
Wiley, Hoboken., 40(2), 51-61.
https://doi.org/10.1002/bdd.2170

Gatarić B, Parojčić J. Application of data mining approach to identify drug subclasses based on solubility and permeability. in Biopharmaceutics & Drug Disposition. 2019;40(2):51-61.
doi:10.1002/bdd.2170 .

Gatarić, Biljana, Parojčić, Jelena, "Application of data mining approach to identify drug subclasses based on solubility and permeability" in Biopharmaceutics & Drug Disposition, 40, no. 2 (2019):51-61,
https://doi.org/10.1002/bdd.2170 . .

TY  - CONF
AU  - Ćirić, Ana
AU  - Đekić, Ljiljana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5370
AB  - Ibuprofen je jedan od najčešće korišćenih nesteroidnih antiinflamatornih
analgetika. Zbog kratkog poluvremena eliminacije (t1/2~2h) neophodna je česta
primena farmaceutskih preparata sa trenutnim oslobađanjem. Radi smanjenja
učestalosti doziranja razmatraju se formulacije sa produženim oslobađanjem.
Biokompatibilni i biodegradabilni kompleksi hitozana sa anjonskim polimerima mogu
potencijalno uticati na kinetiku oslobađanja peroralno primenjenih lekova. Cilj rada bio
je ispitivanje uticaja hidrogelova tipa polielektrolitnog kompleksa hitozan/ksantan na
in vitro kinetiku oslobađanja slabo rastvorljivog ibuprofena.
Pripremljeni su hidrogelovi mešanjem vodenih disperzija hitozana 0,65% (pH
5,6; 0,1M HCl i 0,2M NaOH ) i ksantana 0,65%, na sobnoj temperaturi. Nakon uklanjanja
viška vode, ispiranja i sušenja dobijeni suvi ostatak (hidrogel) je usitnjen, prosejan (sito
600 μm) i upotrebljen za pripremu fizičkih smeša sa ibuprofenom u masenom odnosu
1:1 i 1:2. Smeše su napunjene u kapsule veličine 0 i ispitivan je in vitro profil
oslobađanja u aparaturi sa lopaticom (50 rpm) (Erweka DT70, Nemačka), uz korišćenje
900 ml akceptorskog medijuma (fosfatni pufer pH 7,2) na 37±1°C. Dobijeni hidrogel u
hidratisanom obliku bio je opalescentan, a suvi ostatak bledožute boje. Zahtev
Američke farmakopeje (USP) za in vitro ispitivanje brzine rastvaranja ibuprofena iz
konvencionalnih čvrstih farmaceutskih oblika (tableta) je da se najmanje 80% lekovite
supstance oslobodi nakon 60 min. Kod ispitivane formulacije sa odnosom
hidrogel:ibuprofen 1:1 nakon 60 min oslobođeno je 16,20% lekovite supstance, a kod
formulacije sa odnosom hidrogel:ibuprofen 1:2 utvrđeno je da se nakon 60 min
rastvorilo 9,78% ibuprofena. Dobijeni profili oslobađanja ibuprofena bili su u skladu sa
kinetikom nultog reda (r2> 0,95), a brzina rastvaranja iznosila je 0,416 mg/min (maseni
odnos 1:1) i 0,396 mg/min (maseni odnos 1:2).
Na osnovu dobijenih rezultata može se zaključiti da se korišćenjem hidrogela
tipa polielektrolitnog kompleksa hitozan/ksantan može postići produženo oslobađanje
ibuprofena, pri čemu je ispitivani maseni odnos hidrogela i ibuprofena značajno uticao
na brzinu rastvaranja aktivne supstance.
AB  - Ibuprofen is one of the most frequently used non‐steroidal anti‐inflammatory
analgesics. Due to its short half‐life (t1/2~2h), frequent administration of immediate
release dosage forms is necessary. To reduce the frequency of dosing, prolonged
release formulations are considered. Biocompatible and biodegradable chitosan
complexes with anionic polymers can potentially influence the release kinetics of orally
administered drugs. The aim of this paper was to investigate the influence of
polyelectrolyte complex chitosan/xanthan hydrogels on in vitro release kinetics of
poorly soluble ibuprofen.
Hydrogels were prepared by mixing aqueous dispersions of chitosan 0.65% (pH
5.6, 0.1M HCl and 0.2M NaOH) and xanthan 0.65% at room temperature. After
removing excess water, rinsing and drying, resulting dried residue is crushed, sieved
(sieve 600 μm) and used to prepare physical mixtures with ibuprofen in mass ratio 1:1
and 1:2. The mixtures were filled into capsules size 0 and in vitro release profile in the
paddle apparatus (50 rpm) (Erweka DT70, Germany) was performed using 900 ml of
acceptor medium (phosphate buffer pH 7.2) at 37±1°C.
The resulting hydrogel in hydrated form was opalescent, and dried residue pale
yellow. The US Pharmacopoeia requirement for in vitro dissolution testing of ibuprofen
from tablets is that at least 80% of ibuprofen is released after 60 min. In the
investigated formulation with mass ratio hydrogel:ibuprofen 1:1, after 60 min 16.20%
of ibuprofen was released, and in the formulation with mass ratio hydrogel:ibuprofen
1:2, after 60 min 9.78% of ibuprofen was released. Resulting ibuprofen release profiles
were in accordance with zero order kinetics (r2 >0.95) and dissolution rate was 0.416
mg/min (mass ratio 1:1) and 0.396 mg/min (mass ratio 1:2).
It can be concluded that prolonged release of ibuprofen can be achieved by using
polyelectrolyte complex chitosan/xanthan hydrogels, where in investigated mass ratio
hydrogel:ibuprofen significantly influence the dissolution rate.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Ispitivanje uticaja hidrogela tipa polielektrolitnog kompleksa hitozan/ksantan na in vitro kinetiku oslobađanja ibuprofena
T1  - Investigation of the influence of polyelectrolyte complex chitosan/xanthan hydrogels on the in vitro release kinetics of ibuprofen
VL  - 68
IS  - 3
SP  - 613
EP  - 614
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5370
ER  - 

@conference{
author = "Ćirić, Ana and Đekić, Ljiljana",
year = "2018",
abstract = "Ibuprofen je jedan od najčešće korišćenih nesteroidnih antiinflamatornih
analgetika. Zbog kratkog poluvremena eliminacije (t1/2~2h) neophodna je česta
primena farmaceutskih preparata sa trenutnim oslobađanjem. Radi smanjenja
učestalosti doziranja razmatraju se formulacije sa produženim oslobađanjem.
Biokompatibilni i biodegradabilni kompleksi hitozana sa anjonskim polimerima mogu
potencijalno uticati na kinetiku oslobađanja peroralno primenjenih lekova. Cilj rada bio
je ispitivanje uticaja hidrogelova tipa polielektrolitnog kompleksa hitozan/ksantan na
in vitro kinetiku oslobađanja slabo rastvorljivog ibuprofena.
Pripremljeni su hidrogelovi mešanjem vodenih disperzija hitozana 0,65% (pH
5,6; 0,1M HCl i 0,2M NaOH ) i ksantana 0,65%, na sobnoj temperaturi. Nakon uklanjanja
viška vode, ispiranja i sušenja dobijeni suvi ostatak (hidrogel) je usitnjen, prosejan (sito
600 μm) i upotrebljen za pripremu fizičkih smeša sa ibuprofenom u masenom odnosu
1:1 i 1:2. Smeše su napunjene u kapsule veličine 0 i ispitivan je in vitro profil
oslobađanja u aparaturi sa lopaticom (50 rpm) (Erweka DT70, Nemačka), uz korišćenje
900 ml akceptorskog medijuma (fosfatni pufer pH 7,2) na 37±1°C. Dobijeni hidrogel u
hidratisanom obliku bio je opalescentan, a suvi ostatak bledožute boje. Zahtev
Američke farmakopeje (USP) za in vitro ispitivanje brzine rastvaranja ibuprofena iz
konvencionalnih čvrstih farmaceutskih oblika (tableta) je da se najmanje 80% lekovite
supstance oslobodi nakon 60 min. Kod ispitivane formulacije sa odnosom
hidrogel:ibuprofen 1:1 nakon 60 min oslobođeno je 16,20% lekovite supstance, a kod
formulacije sa odnosom hidrogel:ibuprofen 1:2 utvrđeno je da se nakon 60 min
rastvorilo 9,78% ibuprofena. Dobijeni profili oslobađanja ibuprofena bili su u skladu sa
kinetikom nultog reda (r2> 0,95), a brzina rastvaranja iznosila je 0,416 mg/min (maseni
odnos 1:1) i 0,396 mg/min (maseni odnos 1:2).
Na osnovu dobijenih rezultata može se zaključiti da se korišćenjem hidrogela
tipa polielektrolitnog kompleksa hitozan/ksantan može postići produženo oslobađanje
ibuprofena, pri čemu je ispitivani maseni odnos hidrogela i ibuprofena značajno uticao
na brzinu rastvaranja aktivne supstance., Ibuprofen is one of the most frequently used non‐steroidal anti‐inflammatory
analgesics. Due to its short half‐life (t1/2~2h), frequent administration of immediate
release dosage forms is necessary. To reduce the frequency of dosing, prolonged
release formulations are considered. Biocompatible and biodegradable chitosan
complexes with anionic polymers can potentially influence the release kinetics of orally
administered drugs. The aim of this paper was to investigate the influence of
polyelectrolyte complex chitosan/xanthan hydrogels on in vitro release kinetics of
poorly soluble ibuprofen.
Hydrogels were prepared by mixing aqueous dispersions of chitosan 0.65% (pH
5.6, 0.1M HCl and 0.2M NaOH) and xanthan 0.65% at room temperature. After
removing excess water, rinsing and drying, resulting dried residue is crushed, sieved
(sieve 600 μm) and used to prepare physical mixtures with ibuprofen in mass ratio 1:1
and 1:2. The mixtures were filled into capsules size 0 and in vitro release profile in the
paddle apparatus (50 rpm) (Erweka DT70, Germany) was performed using 900 ml of
acceptor medium (phosphate buffer pH 7.2) at 37±1°C.
The resulting hydrogel in hydrated form was opalescent, and dried residue pale
yellow. The US Pharmacopoeia requirement for in vitro dissolution testing of ibuprofen
from tablets is that at least 80% of ibuprofen is released after 60 min. In the
investigated formulation with mass ratio hydrogel:ibuprofen 1:1, after 60 min 16.20%
of ibuprofen was released, and in the formulation with mass ratio hydrogel:ibuprofen
1:2, after 60 min 9.78% of ibuprofen was released. Resulting ibuprofen release profiles
were in accordance with zero order kinetics (r2 >0.95) and dissolution rate was 0.416
mg/min (mass ratio 1:1) and 0.396 mg/min (mass ratio 1:2).
It can be concluded that prolonged release of ibuprofen can be achieved by using
polyelectrolyte complex chitosan/xanthan hydrogels, where in investigated mass ratio
hydrogel:ibuprofen significantly influence the dissolution rate.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Ispitivanje uticaja hidrogela tipa polielektrolitnog kompleksa hitozan/ksantan na in vitro kinetiku oslobađanja ibuprofena, Investigation of the influence of polyelectrolyte complex chitosan/xanthan hydrogels on the in vitro release kinetics of ibuprofen",
volume = "68",
number = "3",
pages = "613-614",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5370"
}

Ćirić, A.,& Đekić, L.. (2018). Ispitivanje uticaja hidrogela tipa polielektrolitnog kompleksa hitozan/ksantan na in vitro kinetiku oslobađanja ibuprofena. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 68(3), 613-614.
https://hdl.handle.net/21.15107/rcub_farfar_5370

Ćirić A, Đekić L. Ispitivanje uticaja hidrogela tipa polielektrolitnog kompleksa hitozan/ksantan na in vitro kinetiku oslobađanja ibuprofena. in Arhiv za farmaciju. 2018;68(3):613-614.
https://hdl.handle.net/21.15107/rcub_farfar_5370 .

Ćirić, Ana, Đekić, Ljiljana, "Ispitivanje uticaja hidrogela tipa polielektrolitnog kompleksa hitozan/ksantan na in vitro kinetiku oslobađanja ibuprofena" in Arhiv za farmaciju, 68, no. 3 (2018):613-614,
https://hdl.handle.net/21.15107/rcub_farfar_5370 .

TY  - CONF
AU  - Milinković Budinčić, Jelena
AU  - Đekić, Ljiljana
AU  - Petrović, Lidija
AU  - Fraj, Jadranka
AU  - Ćirić, Ana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5369
AB  - INTRODUCTION: The important current focus
in production of cosmetics is usage of vitamin E
(E), a natural antioxidant protective for tissues
from UV radiation, delays photoaging and provide
moisturizing effect. Encapsulation is needed
for its protection from high temperature, oxygen,
and light, during storage, and also for a potential
ability to control its release and delivery. Preparation
of microcapsules of desired characteristics
depends on various factors (size and nature of the
core substance, wall material, techniques and parameters
of encapsulation) [1, 2]. The study aimed
to evaluate chitosan/sodium lauryl ether sulfate
(Ch/SLES) microcapsules with E as a delivery system
for skin care.
MATERIALS AND METHODS: Microcapsules
were prepared by complex coacervation. Initially,
a 20% O/W emulsion with E (10% solution
in medium-chain triglycerides), stabilized with
the mixture of Ch (0.1 %) and SLES [3], was obtained
by Ultra Turrax T25 homogenization. The
emulsion, without or with a crosslinker, formaldehyde
(FA) or glutaraldehyde (GA), was spray
dried. The in vitro release profile of E from the microcapsule
samples (0.1 g) was studied in 100 g of
ethanol 80%, under continuous stirring at room
temperature. The dissolved E in supernatant aliquots
(2 ml) was analyzed during 90 min, by the
Halo DB-20S UV-VIS spectrophotometer.
RESULTS: The obtained release profiles were
analyzed by fi tt ing in different mathematical
models and in all samples correlate the best with
Korsmeyer-Peppas model. The diffusion exponent
n values (0.05-0.23) indicated non-Fickian
diffusion. We assumed that release of E was
based on a combination of rinsing from the surface
of the microcapsules [4] and diffusion
through the capsule wall. For microparticles with
GA, n was the lowest, the release was rapid and
the amount of release of the substance was higher
(i.e., more pronounced rinsing process), compared
with FA and microcapsules without the
crosslinker, where release of E was more controlled
by diffusion.
CONCLUSION: E vitamin release from Ch/
SLES microcapsules followed Korsmeyer-Peppas
kinetics. The selection of the crosslinker influenced
their surface properties, the surface amount and permeability of the capsule wall for E vitamine
diffusion.
PB  - Hungarian Society for Pharmaceutical Sciences
C3  - Acta Pharmaceutica Hungarica, 12th CESPT, Book of Abstracts
T1  - Chitosan/sodium lauryl ether sulfate microcapsules as carriers for vitamin E: in vitro release study
VL  - 88
IS  - 043
SP  - 173
EP  - 174
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5369
ER  - 

@conference{
author = "Milinković Budinčić, Jelena and Đekić, Ljiljana and Petrović, Lidija and Fraj, Jadranka and Ćirić, Ana",
year = "2018",
abstract = "INTRODUCTION: The important current focus
in production of cosmetics is usage of vitamin E
(E), a natural antioxidant protective for tissues
from UV radiation, delays photoaging and provide
moisturizing effect. Encapsulation is needed
for its protection from high temperature, oxygen,
and light, during storage, and also for a potential
ability to control its release and delivery. Preparation
of microcapsules of desired characteristics
depends on various factors (size and nature of the
core substance, wall material, techniques and parameters
of encapsulation) [1, 2]. The study aimed
to evaluate chitosan/sodium lauryl ether sulfate
(Ch/SLES) microcapsules with E as a delivery system
for skin care.
MATERIALS AND METHODS: Microcapsules
were prepared by complex coacervation. Initially,
a 20% O/W emulsion with E (10% solution
in medium-chain triglycerides), stabilized with
the mixture of Ch (0.1 %) and SLES [3], was obtained
by Ultra Turrax T25 homogenization. The
emulsion, without or with a crosslinker, formaldehyde
(FA) or glutaraldehyde (GA), was spray
dried. The in vitro release profile of E from the microcapsule
samples (0.1 g) was studied in 100 g of
ethanol 80%, under continuous stirring at room
temperature. The dissolved E in supernatant aliquots
(2 ml) was analyzed during 90 min, by the
Halo DB-20S UV-VIS spectrophotometer.
RESULTS: The obtained release profiles were
analyzed by fi tt ing in different mathematical
models and in all samples correlate the best with
Korsmeyer-Peppas model. The diffusion exponent
n values (0.05-0.23) indicated non-Fickian
diffusion. We assumed that release of E was
based on a combination of rinsing from the surface
of the microcapsules [4] and diffusion
through the capsule wall. For microparticles with
GA, n was the lowest, the release was rapid and
the amount of release of the substance was higher
(i.e., more pronounced rinsing process), compared
with FA and microcapsules without the
crosslinker, where release of E was more controlled
by diffusion.
CONCLUSION: E vitamin release from Ch/
SLES microcapsules followed Korsmeyer-Peppas
kinetics. The selection of the crosslinker influenced
their surface properties, the surface amount and permeability of the capsule wall for E vitamine
diffusion.",
publisher = "Hungarian Society for Pharmaceutical Sciences",
journal = "Acta Pharmaceutica Hungarica, 12th CESPT, Book of Abstracts",
title = "Chitosan/sodium lauryl ether sulfate microcapsules as carriers for vitamin E: in vitro release study",
volume = "88",
number = "043",
pages = "173-174",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5369"
}

Milinković Budinčić, J., Đekić, L., Petrović, L., Fraj, J.,& Ćirić, A.. (2018). Chitosan/sodium lauryl ether sulfate microcapsules as carriers for vitamin E: in vitro release study. in Acta Pharmaceutica Hungarica, 12th CESPT, Book of Abstracts
Hungarian Society for Pharmaceutical Sciences., 88(043), 173-174.
https://hdl.handle.net/21.15107/rcub_farfar_5369

Milinković Budinčić J, Đekić L, Petrović L, Fraj J, Ćirić A. Chitosan/sodium lauryl ether sulfate microcapsules as carriers for vitamin E: in vitro release study. in Acta Pharmaceutica Hungarica, 12th CESPT, Book of Abstracts. 2018;88(043):173-174.
https://hdl.handle.net/21.15107/rcub_farfar_5369 .

Milinković Budinčić, Jelena, Đekić, Ljiljana, Petrović, Lidija, Fraj, Jadranka, Ćirić, Ana, "Chitosan/sodium lauryl ether sulfate microcapsules as carriers for vitamin E: in vitro release study" in Acta Pharmaceutica Hungarica, 12th CESPT, Book of Abstracts, 88, no. 043 (2018):173-174,
https://hdl.handle.net/21.15107/rcub_farfar_5369 .