TY  - JOUR
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2884
AB  - Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbDbased submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment
VL  - 533
IS  - 2
SP  - 346
EP  - 356
DO  - 10.1016/j.ijpharm.2017.05.070
ER  - 

@article{
author = "Đuriš, Jelena and Đurić, Zorica",
year = "2017",
abstract = "Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbDbased submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment",
volume = "533",
number = "2",
pages = "346-356",
doi = "10.1016/j.ijpharm.2017.05.070"
}

Đuriš, J.,& Đurić, Z.. (2017). Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 533(2), 346-356.
https://doi.org/10.1016/j.ijpharm.2017.05.070

Đuriš J, Đurić Z. Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment. in International Journal of Pharmaceutics. 2017;533(2):346-356.
doi:10.1016/j.ijpharm.2017.05.070 .

Đuriš, Jelena, Đurić, Zorica, "Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment" in International Journal of Pharmaceutics, 533, no. 2 (2017):346-356,
https://doi.org/10.1016/j.ijpharm.2017.05.070 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Kachrimanis, Kyriakos
AU  - Mitrić, Miodrag
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2570
AB  - This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Pharmaceutical Development and Technology
T1  - Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions
VL  - 21
IS  - 3
SP  - 268
EP  - 276
DO  - 10.3109/10837450.2014.996899
ER  - 

@article{
author = "Medarević, Đorđe and Kachrimanis, Kyriakos and Mitrić, Miodrag and Đuriš, Jelena and Đurić, Zorica and Ibrić, Svetlana",
year = "2016",
abstract = "This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Pharmaceutical Development and Technology",
title = "Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions",
volume = "21",
number = "3",
pages = "268-276",
doi = "10.3109/10837450.2014.996899"
}

Medarević, Đ., Kachrimanis, K., Mitrić, M., Đuriš, J., Đurić, Z.,& Ibrić, S.. (2016). Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. in Pharmaceutical Development and Technology
Taylor & Francis Ltd, Abingdon., 21(3), 268-276.
https://doi.org/10.3109/10837450.2014.996899

Medarević Đ, Kachrimanis K, Mitrić M, Đuriš J, Đurić Z, Ibrić S. Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. in Pharmaceutical Development and Technology. 2016;21(3):268-276.
doi:10.3109/10837450.2014.996899 .

Medarević, Đorđe, Kachrimanis, Kyriakos, Mitrić, Miodrag, Đuriš, Jelena, Đurić, Zorica, Ibrić, Svetlana, "Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions" in Pharmaceutical Development and Technology, 21, no. 3 (2016):268-276,
https://doi.org/10.3109/10837450.2014.996899 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Kleinebudde, Peter
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2568
AB  - This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q(10)) and 20 (Q(20)) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Drug Development and Industrial Pharmacy
T1  - Combined application of mixture experimental design and artificial neural networks in the solid dispersion development
VL  - 42
IS  - 3
SP  - 389
EP  - 402
DO  - 10.3109/03639045.2015.1054831
ER  - 

@article{
author = "Medarević, Đorđe and Kleinebudde, Peter and Đuriš, Jelena and Đurić, Zorica and Ibrić, Svetlana",
year = "2016",
abstract = "This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus (R)-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q(10)) and 20 (Q(20)) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Drug Development and Industrial Pharmacy",
title = "Combined application of mixture experimental design and artificial neural networks in the solid dispersion development",
volume = "42",
number = "3",
pages = "389-402",
doi = "10.3109/03639045.2015.1054831"
}

Medarević, Đ., Kleinebudde, P., Đuriš, J., Đurić, Z.,& Ibrić, S.. (2016). Combined application of mixture experimental design and artificial neural networks in the solid dispersion development. in Drug Development and Industrial Pharmacy
Taylor & Francis Ltd, Abingdon., 42(3), 389-402.
https://doi.org/10.3109/03639045.2015.1054831

Medarević Đ, Kleinebudde P, Đuriš J, Đurić Z, Ibrić S. Combined application of mixture experimental design and artificial neural networks in the solid dispersion development. in Drug Development and Industrial Pharmacy. 2016;42(3):389-402.
doi:10.3109/03639045.2015.1054831 .

Medarević, Đorđe, Kleinebudde, Peter, Đuriš, Jelena, Đurić, Zorica, Ibrić, Svetlana, "Combined application of mixture experimental design and artificial neural networks in the solid dispersion development" in Drug Development and Industrial Pharmacy, 42, no. 3 (2016):389-402,
https://doi.org/10.3109/03639045.2015.1054831 . .

TY  - JOUR
AU  - Kaljević, Olivera
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2595
AB  - Compression coating technique has been used in formulation of chronotherapeutic drug delivery systems with pulsatile carvedilol release with polyethylene oxide as controlling release agent. FMEA, risk analysis tool, was applied within Quality by Design approach with aim to detect process and formulation parameters affecting the carvedilol release profile from compression coated tablets. It gives Risk Priority Numbers (RPNs) for each failure mode. Also, using experimental designs, statistical significance of the formulation parameters influence was estimated. High RPNs in case of the lag time as critical quality attribute (CQA) was obtained for polymer molecular weight, compression of coat and low concentration of sodium chloride. For percent of released carvedilol from coated tablets (Q), second CQA, RPNs were high for low concentration of sodium chloride, sodium starch glycolate and crospovidone, polymer molecular weight and also for compression of the tablet coat. Experiments performed according to experimental plans, showed statistically significant influence of Polyox (R) WSR N60K arid sodium chloride concentration on lag time, and concentration of polymer, sodium chloride, mannitol and type of superdisintegrant on Q. These studies demonstrate that FMEA may be a useful tool for Formulation by Design of compression coated tablets.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Drug Delivery Science and Technology
T1  - Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets
VL  - 32
SP  - 56
EP  - 63
DO  - 10.1016/j.jddst.2016.02.004
ER  - 

@article{
author = "Kaljević, Olivera and Đuriš, Jelena and Đurić, Zorica and Ibrić, Svetlana",
year = "2016",
abstract = "Compression coating technique has been used in formulation of chronotherapeutic drug delivery systems with pulsatile carvedilol release with polyethylene oxide as controlling release agent. FMEA, risk analysis tool, was applied within Quality by Design approach with aim to detect process and formulation parameters affecting the carvedilol release profile from compression coated tablets. It gives Risk Priority Numbers (RPNs) for each failure mode. Also, using experimental designs, statistical significance of the formulation parameters influence was estimated. High RPNs in case of the lag time as critical quality attribute (CQA) was obtained for polymer molecular weight, compression of coat and low concentration of sodium chloride. For percent of released carvedilol from coated tablets (Q), second CQA, RPNs were high for low concentration of sodium chloride, sodium starch glycolate and crospovidone, polymer molecular weight and also for compression of the tablet coat. Experiments performed according to experimental plans, showed statistically significant influence of Polyox (R) WSR N60K arid sodium chloride concentration on lag time, and concentration of polymer, sodium chloride, mannitol and type of superdisintegrant on Q. These studies demonstrate that FMEA may be a useful tool for Formulation by Design of compression coated tablets.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Drug Delivery Science and Technology",
title = "Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets",
volume = "32",
pages = "56-63",
doi = "10.1016/j.jddst.2016.02.004"
}

Kaljević, O., Đuriš, J., Đurić, Z.,& Ibrić, S.. (2016). Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets. in Journal of Drug Delivery Science and Technology
Elsevier Science BV, Amsterdam., 32, 56-63.
https://doi.org/10.1016/j.jddst.2016.02.004

Kaljević O, Đuriš J, Đurić Z, Ibrić S. Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets. in Journal of Drug Delivery Science and Technology. 2016;32:56-63.
doi:10.1016/j.jddst.2016.02.004 .

Kaljević, Olivera, Đuriš, Jelena, Đurić, Zorica, Ibrić, Svetlana, "Application of failure mode and effects analysis in quality by design approach for formulation of carvedilol compression coated tablets" in Journal of Drug Delivery Science and Technology, 32 (2016):56-63,
https://doi.org/10.1016/j.jddst.2016.02.004 . .

TY  - JOUR
AU  - Nikolić, Nenad D.
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2492
AB  - This study investigates the use of high molecular weight polyethylene oxide (PEO WSR coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 min were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 min, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline cellulose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinized starch (starch 1500).
AB  - U radu je ispitivan uticaj formulacijskih i procesnih promenljivih na brzinu oslobađanja i mehaničke karakteristike matriks tableta izrađenih sa polietilen oksidom velike molekulske mase (PEO WSR koagulant), kao matriks formirajućim materijalom i visoko rastvoljivom lekovitom supstancom prisutnoj u velikoj dozi, tramadol hidrohloridom. Kao formulacijske promenljive varirane su: udeo polietilen oksidnog polimera (25 ili 35%), vrsta nerastvornog sredstva za dopunjavanje (mikrokristalna celuloza i parcijalno pregelirani skrob), udeo tramadol hidrohlorida (27,8 i 55,6%), količina leka u tableti (100 ili 200 mg). Pritisak kompresije je variran kao procesna promenljiva. Procenat tramadol hidrohlorida rastvoren nakon 30 i 240 min ispitivanja je izabran kao zavisno promenljiva za ispitivanje oslobađanja lekovite supstance, dok je zatezna čvrstoća izabrana kao zavisno promenljiva koja je indikator mehaničkih karakteristika tableta. Izvedena su dva seta eksperimenata, koji odgovaraju 25-2, odnosno 23 eksperimentalnom dizajnu. Tablete su izrađene na simulatoru kompakcije Prester. Simuliran je rad rotacione tablet prese Korch PH336, sa brzinom rotacije 30 rpm, što odgovara kapacitetu od 65000 tableta na sat. Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida pokazalo je da se iz svih formulacija tramadol hidrohlorid oslobađa usporeno, linearnom kinetikom. Najveći uticaj na procenat oslobođenog leka imao je udeo leka u tableti. Sa povećanjem udela leka u tableti, povećavao se i procenat oslobođenog leka u navedenim vremenskih intervalima. Ostali isptivani faktori nisu imali značajan uticaj na brzinu oslobađanja. Ispitivanje mehaničkih karakteristika tableta pokazalo je da na zateznu čvrstoću izrađenih tableta najveći uticaj ima vrsta sredstva za dopunjavanje. Najveće vrednosti zatezne čvrstoće su dobijene u slučaju kada je mikrokristalna celuloza korišćena kao sredstvo za dopunjavanje, kao i kada je procenat polimera u tableti bio na višem nivou. Analiza dobijenih rezultata omogućava pravilan izbor vrste i koncentracije pomoćnih materija u formulaciji matriks tableta sa produženim oslobađanjem izrađenih sa polietilen oksidnim polimerom i visoko rastvorljivom lekovitom supstancom prisutnoj u velikoj dozi.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets
T1  - Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida i mehaničke karakteristike matriks tableta sa produženim oslobađanjem
VL  - 69
IS  - 5
SP  - 503
EP  - 510
DO  - 10.2298/HEMIND140317069N
ER  - 

@article{
author = "Nikolić, Nenad D. and Medarević, Đorđe and Ibrić, Svetlana and Đurić, Zorica",
year = "2015",
abstract = "This study investigates the use of high molecular weight polyethylene oxide (PEO WSR coagulant) for the preparation of sustained release matrix tablets containing high dose, highly water soluble drug, tramadol HCl. Proportion of PEO polymer, type of insoluble filler, proportion of tramadol HCl, amount of drug in tablet, tablet diameter and compression pressure were recognized as critical formulation and process parameters and their influence on drug release and tablet mechanical properties was evaluated. Percentages of tramadol HCl released after 30 and 240 min were selected for evaluation of drug release, while tensile strength was used as indicator of tablet mechanical properties. Only proportion of tramadol HCl exhibits statistically significant effect on percentages of tramadol HCl released after 30 and 240 min, with higher, wherein increasing of the tramadol HCl proportion increased its release rate among the evaluated variables in selected ranges. All of the investigated factors exhibit statistically significant effect on tablets tensile strength, with the largest influence of filler type. Tablets prepared with highly compressible filler (microcrystalline cellulose) exhibit higher tensile strength and therefore better mechanical properties to those prepared with partially pregelatinized starch (starch 1500)., U radu je ispitivan uticaj formulacijskih i procesnih promenljivih na brzinu oslobađanja i mehaničke karakteristike matriks tableta izrađenih sa polietilen oksidom velike molekulske mase (PEO WSR koagulant), kao matriks formirajućim materijalom i visoko rastvoljivom lekovitom supstancom prisutnoj u velikoj dozi, tramadol hidrohloridom. Kao formulacijske promenljive varirane su: udeo polietilen oksidnog polimera (25 ili 35%), vrsta nerastvornog sredstva za dopunjavanje (mikrokristalna celuloza i parcijalno pregelirani skrob), udeo tramadol hidrohlorida (27,8 i 55,6%), količina leka u tableti (100 ili 200 mg). Pritisak kompresije je variran kao procesna promenljiva. Procenat tramadol hidrohlorida rastvoren nakon 30 i 240 min ispitivanja je izabran kao zavisno promenljiva za ispitivanje oslobađanja lekovite supstance, dok je zatezna čvrstoća izabrana kao zavisno promenljiva koja je indikator mehaničkih karakteristika tableta. Izvedena su dva seta eksperimenata, koji odgovaraju 25-2, odnosno 23 eksperimentalnom dizajnu. Tablete su izrađene na simulatoru kompakcije Prester. Simuliran je rad rotacione tablet prese Korch PH336, sa brzinom rotacije 30 rpm, što odgovara kapacitetu od 65000 tableta na sat. Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida pokazalo je da se iz svih formulacija tramadol hidrohlorid oslobađa usporeno, linearnom kinetikom. Najveći uticaj na procenat oslobođenog leka imao je udeo leka u tableti. Sa povećanjem udela leka u tableti, povećavao se i procenat oslobođenog leka u navedenim vremenskih intervalima. Ostali isptivani faktori nisu imali značajan uticaj na brzinu oslobađanja. Ispitivanje mehaničkih karakteristika tableta pokazalo je da na zateznu čvrstoću izrađenih tableta najveći uticaj ima vrsta sredstva za dopunjavanje. Najveće vrednosti zatezne čvrstoće su dobijene u slučaju kada je mikrokristalna celuloza korišćena kao sredstvo za dopunjavanje, kao i kada je procenat polimera u tableti bio na višem nivou. Analiza dobijenih rezultata omogućava pravilan izbor vrste i koncentracije pomoćnih materija u formulaciji matriks tableta sa produženim oslobađanjem izrađenih sa polietilen oksidnim polimerom i visoko rastvorljivom lekovitom supstancom prisutnoj u velikoj dozi.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets, Ispitivanje uticaja faktora formulacije i procesa na oslobađanje tramadol hidrohlorida i mehaničke karakteristike matriks tableta sa produženim oslobađanjem",
volume = "69",
number = "5",
pages = "503-510",
doi = "10.2298/HEMIND140317069N"
}

Nikolić, N. D., Medarević, Đ., Ibrić, S.,& Đurić, Z.. (2015). Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 69(5), 503-510.
https://doi.org/10.2298/HEMIND140317069N

Nikolić ND, Medarević Đ, Ibrić S, Đurić Z. Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets. in Hemijska industrija. 2015;69(5):503-510.
doi:10.2298/HEMIND140317069N .

Nikolić, Nenad D., Medarević, Đorđe, Ibrić, Svetlana, Đurić, Zorica, "Evaluation of formulation and effects of process parameters on drug release and mechanical properties of tramadol hydrochloride sustained release matrix tablets" in Hemijska industrija, 69, no. 5 (2015):503-510,
https://doi.org/10.2298/HEMIND140317069N . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Kachrimanis, Kyriakos
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2321
AB  - In this study binary carbamazepine-hydroxypropyl-beta-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus (R) and two types of hydroxypropyl methylcellulose-Metolose (R) 90SH-100 and Metolose (R) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-B-cyclodextrin for carbamazepine. Evaluation of carbamaze pine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-beta-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-Soluplus (R) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin
VL  - 78
SP  - 273
EP  - 285
DO  - 10.1016/j.ejps.2015.08.001
ER  - 

@article{
author = "Medarević, Đorđe and Kachrimanis, Kyriakos and Đurić, Zorica and Ibrić, Svetlana",
year = "2015",
abstract = "In this study binary carbamazepine-hydroxypropyl-beta-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus (R) and two types of hydroxypropyl methylcellulose-Metolose (R) 90SH-100 and Metolose (R) 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-B-cyclodextrin for carbamazepine. Evaluation of carbamaze pine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-beta-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-beta-cyclodextrin and ternary carbamazepine-hydroxypropyl-beta-cyclodextrin-Soluplus (R) systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin",
volume = "78",
pages = "273-285",
doi = "10.1016/j.ejps.2015.08.001"
}

Medarević, Đ., Kachrimanis, K., Đurić, Z.,& Ibrić, S.. (2015). Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 78, 273-285.
https://doi.org/10.1016/j.ejps.2015.08.001

Medarević Đ, Kachrimanis K, Đurić Z, Ibrić S. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin. in European Journal of Pharmaceutical Sciences. 2015;78:273-285.
doi:10.1016/j.ejps.2015.08.001 .

Medarević, Đorđe, Kachrimanis, Kyriakos, Đurić, Zorica, Ibrić, Svetlana, "Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-beta-cyclodextrin" in European Journal of Pharmaceutical Sciences, 78 (2015):273-285,
https://doi.org/10.1016/j.ejps.2015.08.001 . .

TY  - JOUR
AU  - Nikolić, Nenad D.
AU  - Ibrić, Svetlana
AU  - Medarević, Đorđe
AU  - Đurić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2136
AB  - The aim of this study was establishing design space for robust formulation of hydrophilic extended release matrix tablets with tramadol hydrochloride as highly soluble, high dose drug. In the first part of the study, linear relationship between slope of Higuchi's model (K-h) and tablet surface/tablet volume (SA/V) ratio was confirmed varying drug loading in the range between 27.78 and 55.56% (w/w). Established relationship was tested in the second part of the study using different tablet shapes and sizes. Compression force was varied between 160 MPa and 300 MPa as critical process parameter, while drug loading and polymer concentration were recognized as critical input material attributes. High correlation was established between experimentally observed drug release profiles and drug release profiles predicted using K-h-SA/V relationship. Design space was established, where drug release could be accurately predicted for any drug loading/polymer content/compression force in the investigated range.
PB  - Colegio Farmaceuticos Provincia De Buenos Aires, La Plata
T2  - Latin American Journal of Pharmacy
T1  - Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets
VL  - 33
IS  - 7
SP  - 1131
EP  - 1138
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2136
ER  - 

@article{
author = "Nikolić, Nenad D. and Ibrić, Svetlana and Medarević, Đorđe and Đurić, Zorica",
year = "2014",
abstract = "The aim of this study was establishing design space for robust formulation of hydrophilic extended release matrix tablets with tramadol hydrochloride as highly soluble, high dose drug. In the first part of the study, linear relationship between slope of Higuchi's model (K-h) and tablet surface/tablet volume (SA/V) ratio was confirmed varying drug loading in the range between 27.78 and 55.56% (w/w). Established relationship was tested in the second part of the study using different tablet shapes and sizes. Compression force was varied between 160 MPa and 300 MPa as critical process parameter, while drug loading and polymer concentration were recognized as critical input material attributes. High correlation was established between experimentally observed drug release profiles and drug release profiles predicted using K-h-SA/V relationship. Design space was established, where drug release could be accurately predicted for any drug loading/polymer content/compression force in the investigated range.",
publisher = "Colegio Farmaceuticos Provincia De Buenos Aires, La Plata",
journal = "Latin American Journal of Pharmacy",
title = "Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets",
volume = "33",
number = "7",
pages = "1131-1138",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2136"
}

Nikolić, N. D., Ibrić, S., Medarević, Đ.,& Đurić, Z.. (2014). Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets. in Latin American Journal of Pharmacy
Colegio Farmaceuticos Provincia De Buenos Aires, La Plata., 33(7), 1131-1138.
https://hdl.handle.net/21.15107/rcub_farfar_2136

Nikolić ND, Ibrić S, Medarević Đ, Đurić Z. Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets. in Latin American Journal of Pharmacy. 2014;33(7):1131-1138.
https://hdl.handle.net/21.15107/rcub_farfar_2136 .

Nikolić, Nenad D., Ibrić, Svetlana, Medarević, Đorđe, Đurić, Zorica, "Establishing Design Space for Tramadol HCl Release from Hydrophilic Matrix Tablets" in Latin American Journal of Pharmacy, 33, no. 7 (2014):1131-1138,
https://hdl.handle.net/21.15107/rcub_farfar_2136 .

TY  - JOUR
AU  - Stojković, Aleksandra
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
AU  - Corrigan, Owen I.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2162
AB  - With the development of physiologically based absorption models, there is an increased scientific and regulatory interest in in silico modelling and simulation of drug-drug and drug-food interactions. Clinically significant interactions between ciprofloxacin and metallic compounds are widely documented. In the current study, a previously developed ciprofloxacin-specific in silico absorption model was employed in order to simulate ciprofloxacin/metallic compound interaction observed in vivo. Commercially available software GastroPlus (TM) (Simulations Plus Inc., USA) based on the ACAT model was used for gastrointestinal (GI) simulations. The required input parameters, relating to ciprofloxacin hydrochloride physicochemical and pharmacokinetic characteristics, were experimentally determined, taken from the literature or estimated by GastroPlus (TM). Parameter sensitivity analysis (PSA) was used to assess the importance of selected input parameters (solubility, permeability, stomach and small intestine transit time) in predicting percent drug absorbed. PSA identified solubility and permeability as critical parameters affecting the rate and extent of ciprofloxacin absorption. Using the selected input parameters, it was possible to generate a ciprofloxacin absorption model, without/with metal cation containing preparations co-administration, which matched well the in vivo data available. It was found that reduced ciprofloxacin absorption in the presence of aluminium hydroxide, calcium carbonate or multivitamins/zinc was accounted for by reduced drug solubility. The impact of solubility-permeability interplay on ciprofloxacin absorption can be observed in the ciprofloxacin-aluminium interaction, while in ciprofloxacin-calcium and ciprofloxacin-zinc interactions, effect of solubility was more pronounced. The results obtained indicate that in silico model developed can be successfully used to complement relevant in vitro studies in the simulation of physicochemical ciprofloxacin/metallic compound interactions.
PB  - Springer, New York
T2  - AAPS PharmSciTech
T1  - A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions
VL  - 15
IS  - 2
SP  - 270
EP  - 278
DO  - 10.1208/s12249-013-0055-x
ER  - 

@article{
author = "Stojković, Aleksandra and Parojčić, Jelena and Đurić, Zorica and Corrigan, Owen I.",
year = "2014",
abstract = "With the development of physiologically based absorption models, there is an increased scientific and regulatory interest in in silico modelling and simulation of drug-drug and drug-food interactions. Clinically significant interactions between ciprofloxacin and metallic compounds are widely documented. In the current study, a previously developed ciprofloxacin-specific in silico absorption model was employed in order to simulate ciprofloxacin/metallic compound interaction observed in vivo. Commercially available software GastroPlus (TM) (Simulations Plus Inc., USA) based on the ACAT model was used for gastrointestinal (GI) simulations. The required input parameters, relating to ciprofloxacin hydrochloride physicochemical and pharmacokinetic characteristics, were experimentally determined, taken from the literature or estimated by GastroPlus (TM). Parameter sensitivity analysis (PSA) was used to assess the importance of selected input parameters (solubility, permeability, stomach and small intestine transit time) in predicting percent drug absorbed. PSA identified solubility and permeability as critical parameters affecting the rate and extent of ciprofloxacin absorption. Using the selected input parameters, it was possible to generate a ciprofloxacin absorption model, without/with metal cation containing preparations co-administration, which matched well the in vivo data available. It was found that reduced ciprofloxacin absorption in the presence of aluminium hydroxide, calcium carbonate or multivitamins/zinc was accounted for by reduced drug solubility. The impact of solubility-permeability interplay on ciprofloxacin absorption can be observed in the ciprofloxacin-aluminium interaction, while in ciprofloxacin-calcium and ciprofloxacin-zinc interactions, effect of solubility was more pronounced. The results obtained indicate that in silico model developed can be successfully used to complement relevant in vitro studies in the simulation of physicochemical ciprofloxacin/metallic compound interactions.",
publisher = "Springer, New York",
journal = "AAPS PharmSciTech",
title = "A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions",
volume = "15",
number = "2",
pages = "270-278",
doi = "10.1208/s12249-013-0055-x"
}

Stojković, A., Parojčić, J., Đurić, Z.,& Corrigan, O. I.. (2014). A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions. in AAPS PharmSciTech
Springer, New York., 15(2), 270-278.
https://doi.org/10.1208/s12249-013-0055-x

Stojković A, Parojčić J, Đurić Z, Corrigan OI. A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions. in AAPS PharmSciTech. 2014;15(2):270-278.
doi:10.1208/s12249-013-0055-x .

Stojković, Aleksandra, Parojčić, Jelena, Đurić, Zorica, Corrigan, Owen I., "A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride/Metallic Compound Interactions" in AAPS PharmSciTech, 15, no. 2 (2014):270-278,
https://doi.org/10.1208/s12249-013-0055-x . .

TY  - JOUR
AU  - Stojković, Aleksandra
AU  - Tajber, Lidia
AU  - Paluch, Krzysztof J.
AU  - Đurić, Zorica
AU  - Parojčić, Jelena
AU  - Corrigan, Owen I.
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2161
AB  - Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)(2)(Cl)(2)(ciprofloxacin)(2) x nH(2)O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.
PB  - Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb
T2  - Acta Pharmaceutica
T1  - Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution
VL  - 64
IS  - 1
SP  - 77
EP  - 88
DO  - 10.2478/acph-2014-0007
ER  - 

@article{
author = "Stojković, Aleksandra and Tajber, Lidia and Paluch, Krzysztof J. and Đurić, Zorica and Parojčić, Jelena and Corrigan, Owen I.",
year = "2014",
abstract = "Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)(2)(Cl)(2)(ciprofloxacin)(2) x nH(2)O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.",
publisher = "Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb",
journal = "Acta Pharmaceutica",
title = "Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution",
volume = "64",
number = "1",
pages = "77-88",
doi = "10.2478/acph-2014-0007"
}

Stojković, A., Tajber, L., Paluch, K. J., Đurić, Z., Parojčić, J.,& Corrigan, O. I.. (2014). Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution. in Acta Pharmaceutica
Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb., 64(1), 77-88.
https://doi.org/10.2478/acph-2014-0007

Stojković A, Tajber L, Paluch KJ, Đurić Z, Parojčić J, Corrigan OI. Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution. in Acta Pharmaceutica. 2014;64(1):77-88.
doi:10.2478/acph-2014-0007 .

Stojković, Aleksandra, Tajber, Lidia, Paluch, Krzysztof J., Đurić, Zorica, Parojčić, Jelena, Corrigan, Owen I., "Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: Comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution" in Acta Pharmaceutica, 64, no. 1 (2014):77-88,
https://doi.org/10.2478/acph-2014-0007 . .

TY  - JOUR
AU  - Stojković, Aleksandra
AU  - Tajber, Lidia
AU  - Đurić, Zorica
AU  - Corrigan, Owen I.
AU  - Parojčić, Jelena
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2097
AB  - In vitro dissolution testing has long been used as a tool in drug product development and quality control, however, its potential for drug/food and drug/drug interactions has not yet been filly exploited. Ciprofloxacin absorption in vivo may be reduced when co-administered with different metallic compounds. In the present study, in vitro ciprofloxacin solubility and drug dissolution from tablets were performed in the reactive media containing zinc chloride in order to simulate ciprofloxacin/zinc interaction observed in vivo. The precipitates collected from dissolution vessel and from mixture containing ciprofloxacin-hydrochloride and zinc-chloride were investigated using XRPD, TGA, DCS, FTIR. Ciprofloxacin-hydrochloride solubility and drug dissolution from tablet were reduced in aqueous media containing increasing amounts of zinc-chloride. Complex with probable chemical structure kin [cfH(2)](2)center dot[ZnCl4]center dot 2H(2)O was generated in the presence of high concentrations of ciprofloxacin-hydrochloride and zinc-chloride, indicating that small volume dissolution experiments can be useful in biopharmaceutical characterisation of drug interaction studies.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Drug Delivery Science and Technology
T1  - In vitro simulation of drug interaction: ciprofloxacin/zinc chloride
VL  - 24
IS  - 2
SP  - 229
EP  - 233
DO  - 10.1016/S1773-2247(14)50037-8
ER  - 

@article{
author = "Stojković, Aleksandra and Tajber, Lidia and Đurić, Zorica and Corrigan, Owen I. and Parojčić, Jelena",
year = "2014",
abstract = "In vitro dissolution testing has long been used as a tool in drug product development and quality control, however, its potential for drug/food and drug/drug interactions has not yet been filly exploited. Ciprofloxacin absorption in vivo may be reduced when co-administered with different metallic compounds. In the present study, in vitro ciprofloxacin solubility and drug dissolution from tablets were performed in the reactive media containing zinc chloride in order to simulate ciprofloxacin/zinc interaction observed in vivo. The precipitates collected from dissolution vessel and from mixture containing ciprofloxacin-hydrochloride and zinc-chloride were investigated using XRPD, TGA, DCS, FTIR. Ciprofloxacin-hydrochloride solubility and drug dissolution from tablet were reduced in aqueous media containing increasing amounts of zinc-chloride. Complex with probable chemical structure kin [cfH(2)](2)center dot[ZnCl4]center dot 2H(2)O was generated in the presence of high concentrations of ciprofloxacin-hydrochloride and zinc-chloride, indicating that small volume dissolution experiments can be useful in biopharmaceutical characterisation of drug interaction studies.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Drug Delivery Science and Technology",
title = "In vitro simulation of drug interaction: ciprofloxacin/zinc chloride",
volume = "24",
number = "2",
pages = "229-233",
doi = "10.1016/S1773-2247(14)50037-8"
}

Stojković, A., Tajber, L., Đurić, Z., Corrigan, O. I.,& Parojčić, J.. (2014). In vitro simulation of drug interaction: ciprofloxacin/zinc chloride. in Journal of Drug Delivery Science and Technology
Elsevier Science BV, Amsterdam., 24(2), 229-233.
https://doi.org/10.1016/S1773-2247(14)50037-8

Stojković A, Tajber L, Đurić Z, Corrigan OI, Parojčić J. In vitro simulation of drug interaction: ciprofloxacin/zinc chloride. in Journal of Drug Delivery Science and Technology. 2014;24(2):229-233.
doi:10.1016/S1773-2247(14)50037-8 .

Stojković, Aleksandra, Tajber, Lidia, Đurić, Zorica, Corrigan, Owen I., Parojčić, Jelena, "In vitro simulation of drug interaction: ciprofloxacin/zinc chloride" in Journal of Drug Delivery Science and Technology, 24, no. 2 (2014):229-233,
https://doi.org/10.1016/S1773-2247(14)50037-8 . .

TY  - JOUR
AU  - Đokić, Marija
AU  - Đuriš, Jelena
AU  - Solomun, Ljiljana
AU  - Kachrimanis, Kyriakos
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2159
AB  - The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of alpha polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2((4-1)) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2((3-1)) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5 mu m, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.
PB  - Inst Chemical Engineers, Rugby
T2  - Chemical Engineering Research & Design
T1  - The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach
VL  - 92
IS  - 3
SP  - 500
EP  - 508
DO  - 10.1016/j.cherd.2013.09.011
ER  - 

@article{
author = "Đokić, Marija and Đuriš, Jelena and Solomun, Ljiljana and Kachrimanis, Kyriakos and Đurić, Zorica and Ibrić, Svetlana",
year = "2014",
abstract = "The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of alpha polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2((4-1)) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2((3-1)) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5 mu m, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.",
publisher = "Inst Chemical Engineers, Rugby",
journal = "Chemical Engineering Research & Design",
title = "The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach",
volume = "92",
number = "3",
pages = "500-508",
doi = "10.1016/j.cherd.2013.09.011"
}

Đokić, M., Đuriš, J., Solomun, L., Kachrimanis, K., Đurić, Z.,& Ibrić, S.. (2014). The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach. in Chemical Engineering Research & Design
Inst Chemical Engineers, Rugby., 92(3), 500-508.
https://doi.org/10.1016/j.cherd.2013.09.011

Đokić M, Đuriš J, Solomun L, Kachrimanis K, Đurić Z, Ibrić S. The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach. in Chemical Engineering Research & Design. 2014;92(3):500-508.
doi:10.1016/j.cherd.2013.09.011 .

Đokić, Marija, Đuriš, Jelena, Solomun, Ljiljana, Kachrimanis, Kyriakos, Đurić, Zorica, Ibrić, Svetlana, "The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach" in Chemical Engineering Research & Design, 92, no. 3 (2014):500-508,
https://doi.org/10.1016/j.cherd.2013.09.011 . .

TY  - JOUR
AU  - Miletić, Tijana
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2188
AB  - The aim of this study was to investigate the usefulness of combined application of quality by design tools such as central composite design (CCD), response surface methodology (RSM), and artificial neural networks (ANN) in the characterization, modeling, and optimizaton of spray drying of a poorly soluble drug : cyclodextrin complex. Models were developed by RSM and ANN from different pools of data. The model with best predictability was the ANN multilayer perceptron (MLP)1 model developed from the largest group of data (R-2 for response yield 0.854, moisture content 0.886). On the other hand, analysis of equations derived from the application of RSM contributed in better understanding the complex relationships between input and output variables. By application of a desirability function approach, optimal process parameters that resulted in the best process yield (86%) and minimal moisture content in the powder (3.3%) were established (25% feed concentration, 180 degrees C inlet air temperature, 10% pump speed).
PB  - Taylor & Francis Inc, Philadelphia
T2  - Drying Technology
T1  - Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes
VL  - 32
IS  - 2
SP  - 167
EP  - 179
DO  - 10.1080/07373937.2013.811593
ER  - 

@article{
author = "Miletić, Tijana and Ibrić, Svetlana and Đurić, Zorica",
year = "2014",
abstract = "The aim of this study was to investigate the usefulness of combined application of quality by design tools such as central composite design (CCD), response surface methodology (RSM), and artificial neural networks (ANN) in the characterization, modeling, and optimizaton of spray drying of a poorly soluble drug : cyclodextrin complex. Models were developed by RSM and ANN from different pools of data. The model with best predictability was the ANN multilayer perceptron (MLP)1 model developed from the largest group of data (R-2 for response yield 0.854, moisture content 0.886). On the other hand, analysis of equations derived from the application of RSM contributed in better understanding the complex relationships between input and output variables. By application of a desirability function approach, optimal process parameters that resulted in the best process yield (86%) and minimal moisture content in the powder (3.3%) were established (25% feed concentration, 180 degrees C inlet air temperature, 10% pump speed).",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Drying Technology",
title = "Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes",
volume = "32",
number = "2",
pages = "167-179",
doi = "10.1080/07373937.2013.811593"
}

Miletić, T., Ibrić, S.,& Đurić, Z.. (2014). Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes. in Drying Technology
Taylor & Francis Inc, Philadelphia., 32(2), 167-179.
https://doi.org/10.1080/07373937.2013.811593

Miletić T, Ibrić S, Đurić Z. Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes. in Drying Technology. 2014;32(2):167-179.
doi:10.1080/07373937.2013.811593 .

Miletić, Tijana, Ibrić, Svetlana, Đurić, Zorica, "Combined Application of Experimental Design and Artificial Neural Networks in Modeling and Characterization of Spray Drying Drug: Cyclodextrin Complexes" in Drying Technology, 32, no. 2 (2014):167-179,
https://doi.org/10.1080/07373937.2013.811593 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Ioannis, Nikolakakis
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
AU  - Kachrimanis, Kyriakos
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2185
AB  - ObjectivesThis study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. MethodsPrepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Key findingsSolid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ:Poloxamer 407=1:1 showing the highest increase in CBZ release rate. ConclusionsInteractions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Pharmacy and Pharmacology
T1  - Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design
VL  - 66
IS  - 2
SP  - 232
EP  - 243
DO  - 10.1111/jphp.12199
ER  - 

@article{
author = "Đuriš, Jelena and Ioannis, Nikolakakis and Ibrić, Svetlana and Đurić, Zorica and Kachrimanis, Kyriakos",
year = "2014",
abstract = "ObjectivesThis study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. MethodsPrepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Key findingsSolid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ:Poloxamer 407=1:1 showing the highest increase in CBZ release rate. ConclusionsInteractions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Pharmacy and Pharmacology",
title = "Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design",
volume = "66",
number = "2",
pages = "232-243",
doi = "10.1111/jphp.12199"
}

Đuriš, J., Ioannis, N., Ibrić, S., Đurić, Z.,& Kachrimanis, K.. (2014). Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design. in Journal of Pharmacy and Pharmacology
Wiley-Blackwell, Hoboken., 66(2), 232-243.
https://doi.org/10.1111/jphp.12199

Đuriš J, Ioannis N, Ibrić S, Đurić Z, Kachrimanis K. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design. in Journal of Pharmacy and Pharmacology. 2014;66(2):232-243.
doi:10.1111/jphp.12199 .

Đuriš, Jelena, Ioannis, Nikolakakis, Ibrić, Svetlana, Đurić, Zorica, Kachrimanis, Kyriakos, "Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design" in Journal of Pharmacy and Pharmacology, 66, no. 2 (2014):232-243,
https://doi.org/10.1111/jphp.12199 . .

TY  - JOUR
AU  - Petrović, Aleksandra
AU  - Petricević, Sasa M.
AU  - Ristić, Slavica M.
AU  - Ibrić, Svetlana
AU  - Simić, Slobodanka
AU  - Đurić, Zorica
AU  - Popović, Radmila
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2002
AB  - Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin (R) 350, tablets Purdue Frederic, Canada (R-II). Results: Calculated release rate constants and the f2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T-max, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest C-max (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). Discussion and conclusion: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.
PB  - Informa Healthcare, London
T2  - Drug Development and Industrial Pharmacy
T1  - Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms
VL  - 39
IS  - 6
SP  - 889
EP  - 900
DO  - 10.3109/03639045.2012.713364
ER  - 

@article{
author = "Petrović, Aleksandra and Petricević, Sasa M. and Ristić, Slavica M. and Ibrić, Svetlana and Simić, Slobodanka and Đurić, Zorica and Popović, Radmila",
year = "2013",
abstract = "Objective: The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied. Materials and methods: Three modified-release formulations of aminophylline consisted of Carbopol (R) 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin (R) 350, tablets Purdue Frederic, Canada (R-II). Results: Calculated release rate constants and the f2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher T-max, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest C-max (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L). Discussion and conclusion: The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.",
publisher = "Informa Healthcare, London",
journal = "Drug Development and Industrial Pharmacy",
title = "Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms",
volume = "39",
number = "6",
pages = "889-900",
doi = "10.3109/03639045.2012.713364"
}

Petrović, A., Petricević, S. M., Ristić, S. M., Ibrić, S., Simić, S., Đurić, Z.,& Popović, R.. (2013). Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms. in Drug Development and Industrial Pharmacy
Informa Healthcare, London., 39(6), 889-900.
https://doi.org/10.3109/03639045.2012.713364

Petrović A, Petricević SM, Ristić SM, Ibrić S, Simić S, Đurić Z, Popović R. Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms. in Drug Development and Industrial Pharmacy. 2013;39(6):889-900.
doi:10.3109/03639045.2012.713364 .

Petrović, Aleksandra, Petricević, Sasa M., Ristić, Slavica M., Ibrić, Svetlana, Simić, Slobodanka, Đurić, Zorica, Popović, Radmila, "Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms" in Drug Development and Industrial Pharmacy, 39, no. 6 (2013):889-900,
https://doi.org/10.3109/03639045.2012.713364 . .

TY  - JOUR
AU  - Medarević, Đorđe
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2053
AB  - A growing number of newly synthesized drugs exhibit low aqueous solubility, leading to poor bioavailability. Therefore, improving drug solubility and dissolution rate became one of the greatest challenges during formulation development. Solid dispersions formulation is one of the commonly investigated techniques for improving solubility of poorly soluble drugs. Solid dispersions are dispersions of one or more drugs in an inert carrier (matrix) in the solid state prepared by melting, solvent, or melting-solvent method. Generation of drug's amorphous form, drug dissolution within the matrix, reducing particle size and agglomeration, improved wetting and drug solubilization by the carrier molecules are the main mechanisms contributing to the improvement of solubility and dissolution rate by solid dispersions formulation. However, during 50 years research of this field, only a few such preparations appeared on the market. High drug: excipients ratio, difficulties in process scale up, poor reproducibility of physico­chemical characteristics and problems in ensuring of long term stability are the main problems in solid dispersions formulation. It is considered that the development and improvement of industrially feasible techniques, such as hot-melt extrusion and spray drying and wider availability of techniques for physic-chemical characterization will contribute to wider application of solid dispersion technique in drugs manufacturing.
AB  - Sve veći broj novosintetisanih lekovitih supstanci pokazuje nisku rastvorljivost u vodi, što dovodi do problema u biološkoj raspoloživosti. Stoga, poboljšanje rastvorljivosti i brzine rastvaranja predstavlja jedan od najvećih izazova prilikom razvoja formulacije. Izrada čvrstih disperzija jedna je od najviše istraživanih tehnika za poboljšanje rastvorljivosti teško rastvornih lekovitih supstanci. Čvrste disperzije predstavljaju disperzije jedne ili više lekovitih supstanci u inertnom nosaču (matriksu), u čvrstom stanju, dobijene metodom topljenja, uz korišćenje rastvarača ili kombinacijom ovih metoda. Nastanak amorfne forme leka, rastvaranje leka u matriksu, smanjenje veličine čestica i njihove aglomeracije, poboljšano kvašenje i solubilizacija molekulima nosača, glavni su mehanizmi koji doprinose poboljšanju rastvorljivosti i brzine rastvaranja leka formulacijom čvrstih disperzija. Ipak, za više od 50 godina istraživanja na ovom polju, svega nekoliko preparata sa čvrstim disperzijama leka pojavilo se na tržištu. Visok odnos lekovita supstanca: ekscipijens, otežan prenos proizvodnje sa laboratorijskog na industrijski nivo, slaba reproduktivnost fizičko-hemijskih karakteristika i problemi sa obezbeđivanjem dugoročne stabilnosti, glavni su problemi u formulaciji čvrstih disperzija. Smatra se da će razvoj i usavršavanje industrijski primenljivih tehnika izrade, kao što su ekstruzija topljenjem i sušenje raspršivanjem, kao i sve veća dostupnost tehnika za fizičko- hemijsku karakterizaciju, doprineti široj primeni tehnike čvrstih disperzija u proizvodnji lekova.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization
T1  - Primena čvrstih disperzija u farmaceutskoj tehnologiji - postupci izrade i metode karakterizacije
VL  - 63
IS  - 6
SP  - 473
EP  - 493
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2053
ER  - 

@article{
author = "Medarević, Đorđe and Ibrić, Svetlana and Đuriš, Jelena and Đurić, Zorica",
year = "2013",
abstract = "A growing number of newly synthesized drugs exhibit low aqueous solubility, leading to poor bioavailability. Therefore, improving drug solubility and dissolution rate became one of the greatest challenges during formulation development. Solid dispersions formulation is one of the commonly investigated techniques for improving solubility of poorly soluble drugs. Solid dispersions are dispersions of one or more drugs in an inert carrier (matrix) in the solid state prepared by melting, solvent, or melting-solvent method. Generation of drug's amorphous form, drug dissolution within the matrix, reducing particle size and agglomeration, improved wetting and drug solubilization by the carrier molecules are the main mechanisms contributing to the improvement of solubility and dissolution rate by solid dispersions formulation. However, during 50 years research of this field, only a few such preparations appeared on the market. High drug: excipients ratio, difficulties in process scale up, poor reproducibility of physico­chemical characteristics and problems in ensuring of long term stability are the main problems in solid dispersions formulation. It is considered that the development and improvement of industrially feasible techniques, such as hot-melt extrusion and spray drying and wider availability of techniques for physic-chemical characterization will contribute to wider application of solid dispersion technique in drugs manufacturing., Sve veći broj novosintetisanih lekovitih supstanci pokazuje nisku rastvorljivost u vodi, što dovodi do problema u biološkoj raspoloživosti. Stoga, poboljšanje rastvorljivosti i brzine rastvaranja predstavlja jedan od najvećih izazova prilikom razvoja formulacije. Izrada čvrstih disperzija jedna je od najviše istraživanih tehnika za poboljšanje rastvorljivosti teško rastvornih lekovitih supstanci. Čvrste disperzije predstavljaju disperzije jedne ili više lekovitih supstanci u inertnom nosaču (matriksu), u čvrstom stanju, dobijene metodom topljenja, uz korišćenje rastvarača ili kombinacijom ovih metoda. Nastanak amorfne forme leka, rastvaranje leka u matriksu, smanjenje veličine čestica i njihove aglomeracije, poboljšano kvašenje i solubilizacija molekulima nosača, glavni su mehanizmi koji doprinose poboljšanju rastvorljivosti i brzine rastvaranja leka formulacijom čvrstih disperzija. Ipak, za više od 50 godina istraživanja na ovom polju, svega nekoliko preparata sa čvrstim disperzijama leka pojavilo se na tržištu. Visok odnos lekovita supstanca: ekscipijens, otežan prenos proizvodnje sa laboratorijskog na industrijski nivo, slaba reproduktivnost fizičko-hemijskih karakteristika i problemi sa obezbeđivanjem dugoročne stabilnosti, glavni su problemi u formulaciji čvrstih disperzija. Smatra se da će razvoj i usavršavanje industrijski primenljivih tehnika izrade, kao što su ekstruzija topljenjem i sušenje raspršivanjem, kao i sve veća dostupnost tehnika za fizičko- hemijsku karakterizaciju, doprineti široj primeni tehnike čvrstih disperzija u proizvodnji lekova.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization, Primena čvrstih disperzija u farmaceutskoj tehnologiji - postupci izrade i metode karakterizacije",
volume = "63",
number = "6",
pages = "473-493",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2053"
}

Medarević, Đ., Ibrić, S., Đuriš, J.,& Đurić, Z.. (2013). Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 63(6), 473-493.
https://hdl.handle.net/21.15107/rcub_farfar_2053

Medarević Đ, Ibrić S, Đuriš J, Đurić Z. Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization. in Arhiv za farmaciju. 2013;63(6):473-493.
https://hdl.handle.net/21.15107/rcub_farfar_2053 .

Medarević, Đorđe, Ibrić, Svetlana, Đuriš, Jelena, Đurić, Zorica, "Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization" in Arhiv za farmaciju, 63, no. 6 (2013):473-493,
https://hdl.handle.net/21.15107/rcub_farfar_2053 .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Medarević, Đorđe
AU  - Krstić, Marko
AU  - Đurić, Zorica
AU  - Ibrić, Svetlana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1996
AB  - This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to PlackettBurman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed.
PB  - Elsevier Science Inc, New York
T2  - Journal of Pharmaceutical Sciences
T1  - Application of quality by design concepts in the development of fluidized bed granulation and tableting processes
VL  - 102
IS  - 6
SP  - 1869
EP  - 1882
DO  - 10.1002/jps.23530
ER  - 

@article{
author = "Đuriš, Jelena and Medarević, Đorđe and Krstić, Marko and Đurić, Zorica and Ibrić, Svetlana",
year = "2013",
abstract = "This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to PlackettBurman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed.",
publisher = "Elsevier Science Inc, New York",
journal = "Journal of Pharmaceutical Sciences",
title = "Application of quality by design concepts in the development of fluidized bed granulation and tableting processes",
volume = "102",
number = "6",
pages = "1869-1882",
doi = "10.1002/jps.23530"
}

Đuriš, J., Medarević, Đ., Krstić, M., Đurić, Z.,& Ibrić, S.. (2013). Application of quality by design concepts in the development of fluidized bed granulation and tableting processes. in Journal of Pharmaceutical Sciences
Elsevier Science Inc, New York., 102(6), 1869-1882.
https://doi.org/10.1002/jps.23530

Đuriš J, Medarević Đ, Krstić M, Đurić Z, Ibrić S. Application of quality by design concepts in the development of fluidized bed granulation and tableting processes. in Journal of Pharmaceutical Sciences. 2013;102(6):1869-1882.
doi:10.1002/jps.23530 .

Đuriš, Jelena, Medarević, Đorđe, Krstić, Marko, Đurić, Zorica, Ibrić, Svetlana, "Application of quality by design concepts in the development of fluidized bed granulation and tableting processes" in Journal of Pharmaceutical Sciences, 102, no. 6 (2013):1869-1882,
https://doi.org/10.1002/jps.23530 . .

TY  - CHAP
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2024
AB  - This chapter presents a review of the possible applications of methods based on neural computing in pharmaceutical products and process development. Some of the methods described are used for classification purposes, whereas others can be applied to modeling and optimization, or even induction of rules. Basic concepts of each method are theoretically described, followed by examples of their application in pharmaceutical technology. A theoretical background aims to provide a better understanding of the methods and is based upon their most important features. Examples should encourage the reader to embrace the above-mentioned methods and use them to complement conventional statistical methods for classification and regression.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Neural computing in pharmaceutical products and process development
SP  - 91
EP  - 175
DO  - 10.1016/B978-1-907568-27-5.50005-6
ER  - 

@inbook{
author = "Đuriš, Jelena and Ibrić, Svetlana and Đurić, Zorica",
year = "2013",
abstract = "This chapter presents a review of the possible applications of methods based on neural computing in pharmaceutical products and process development. Some of the methods described are used for classification purposes, whereas others can be applied to modeling and optimization, or even induction of rules. Basic concepts of each method are theoretically described, followed by examples of their application in pharmaceutical technology. A theoretical background aims to provide a better understanding of the methods and is based upon their most important features. Examples should encourage the reader to embrace the above-mentioned methods and use them to complement conventional statistical methods for classification and regression.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Neural computing in pharmaceutical products and process development",
pages = "91-175",
doi = "10.1016/B978-1-907568-27-5.50005-6"
}

Đuriš, J., Ibrić, S.,& Đurić, Z.. (2013). Neural computing in pharmaceutical products and process development. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 91-175.
https://doi.org/10.1016/B978-1-907568-27-5.50005-6

Đuriš J, Ibrić S, Đurić Z. Neural computing in pharmaceutical products and process development. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:91-175.
doi:10.1016/B978-1-907568-27-5.50005-6 .

Đuriš, Jelena, Ibrić, Svetlana, Đurić, Zorica, "Neural computing in pharmaceutical products and process development" in Computer-Aided Applications in Pharmaceutical Technology (2013):91-175,
https://doi.org/10.1016/B978-1-907568-27-5.50005-6 . .

TY  - CHAP
AU  - Mašić, Ivana
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2019
AB  - This chapter introduces the concept of computational fluid dynamics (CFD) and its applications in pharmaceutical technology. Basic theoretical explanations on the mathematics of fluid flow and numerical grids are provided. CFD is a versatile tool that is mainly used in complex dynamical process characterization. Examples of CFD applications in development of inhalers, analysis of dissolution apparatus hydrodynamics, and fluidized bed process simulations are presented.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Computational fluid dynamics: Applications in pharmaceutical technology
SP  - 233
EP  - 259
DO  - 10.1016/B978-1-907568-27-5.50007-X
ER  - 

@inbook{
author = "Mašić, Ivana and Parojčić, Jelena and Đurić, Zorica",
year = "2013",
abstract = "This chapter introduces the concept of computational fluid dynamics (CFD) and its applications in pharmaceutical technology. Basic theoretical explanations on the mathematics of fluid flow and numerical grids are provided. CFD is a versatile tool that is mainly used in complex dynamical process characterization. Examples of CFD applications in development of inhalers, analysis of dissolution apparatus hydrodynamics, and fluidized bed process simulations are presented.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Computational fluid dynamics: Applications in pharmaceutical technology",
pages = "233-259",
doi = "10.1016/B978-1-907568-27-5.50007-X"
}

Mašić, I., Parojčić, J.,& Đurić, Z.. (2013). Computational fluid dynamics: Applications in pharmaceutical technology. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 233-259.
https://doi.org/10.1016/B978-1-907568-27-5.50007-X

Mašić I, Parojčić J, Đurić Z. Computational fluid dynamics: Applications in pharmaceutical technology. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:233-259.
doi:10.1016/B978-1-907568-27-5.50007-X .

Mašić, Ivana, Parojčić, Jelena, Đurić, Zorica, "Computational fluid dynamics: Applications in pharmaceutical technology" in Computer-Aided Applications in Pharmaceutical Technology (2013):233-259,
https://doi.org/10.1016/B978-1-907568-27-5.50007-X . .

TY  - CHAP
AU  - Grbić, Sandra
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2022
AB  - This chapter introduces the concept of gastrointestinal absorption simulation using in silico methodology. Parameters used for model construction and the sensitivity predicted pharmacokinetic responses to various input parameters are described. Virtual trials for in silico modeling of drug absorption are presented. The influence of food on drug absorption, as well as correlation between the in vitro and in vivo results, are also addressed, followed by biowaiver considerations. Numerous examples are provided throughout the chapter.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Computer-aided biopharmaceutical characterization: Gastrointestinal absorption simulation
SP  - 177
EP  - 232
DO  - 10.1016/B978-1-907568-27-5.50006-8
ER  - 

@inbook{
author = "Grbić, Sandra and Parojčić, Jelena and Đurić, Zorica",
year = "2013",
abstract = "This chapter introduces the concept of gastrointestinal absorption simulation using in silico methodology. Parameters used for model construction and the sensitivity predicted pharmacokinetic responses to various input parameters are described. Virtual trials for in silico modeling of drug absorption are presented. The influence of food on drug absorption, as well as correlation between the in vitro and in vivo results, are also addressed, followed by biowaiver considerations. Numerous examples are provided throughout the chapter.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Computer-aided biopharmaceutical characterization: Gastrointestinal absorption simulation",
pages = "177-232",
doi = "10.1016/B978-1-907568-27-5.50006-8"
}

Grbić, S., Parojčić, J.,& Đurić, Z.. (2013). Computer-aided biopharmaceutical characterization: Gastrointestinal absorption simulation. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 177-232.
https://doi.org/10.1016/B978-1-907568-27-5.50006-8

Grbić S, Parojčić J, Đurić Z. Computer-aided biopharmaceutical characterization: Gastrointestinal absorption simulation. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:177-232.
doi:10.1016/B978-1-907568-27-5.50006-8 .

Grbić, Sandra, Parojčić, Jelena, Đurić, Zorica, "Computer-aided biopharmaceutical characterization: Gastrointestinal absorption simulation" in Computer-Aided Applications in Pharmaceutical Technology (2013):177-232,
https://doi.org/10.1016/B978-1-907568-27-5.50006-8 . .

TY  - CHAP
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2034
AB  - This first chapter introduces the concept of quality-by-design (QbD) and its role in pharmaceutical product development. QbD assures the quality of a pharmaceutical product through scientific development and risk management tools, and will eventually enable real-time release, regardless of the formulation type. Several guidelines on pharmaceutical development, quality risk management, and pharmaceutical quality systems are presented that are applicable throughout the product lifecycle. Design space appointment and control strategies for risk management are introduced. The meaning of the QbD concept is presented from both regulatory and manufacturers' points of view. Several illustrative examples are provided to facilitate the understanding of the QbD concept and ease of its application.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Quality-by-design in pharmaceutical development
SP  - 1
EP  - 16
DO  - 10.1016/B978-1-907568-27-5.50001-9
ER  - 

@inbook{
author = "Đuriš, Jelena and Ibrić, Svetlana and Đurić, Zorica",
year = "2013",
abstract = "This first chapter introduces the concept of quality-by-design (QbD) and its role in pharmaceutical product development. QbD assures the quality of a pharmaceutical product through scientific development and risk management tools, and will eventually enable real-time release, regardless of the formulation type. Several guidelines on pharmaceutical development, quality risk management, and pharmaceutical quality systems are presented that are applicable throughout the product lifecycle. Design space appointment and control strategies for risk management are introduced. The meaning of the QbD concept is presented from both regulatory and manufacturers' points of view. Several illustrative examples are provided to facilitate the understanding of the QbD concept and ease of its application.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Quality-by-design in pharmaceutical development",
pages = "1-16",
doi = "10.1016/B978-1-907568-27-5.50001-9"
}

Đuriš, J., Ibrić, S.,& Đurić, Z.. (2013). Quality-by-design in pharmaceutical development. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 1-16.
https://doi.org/10.1016/B978-1-907568-27-5.50001-9

Đuriš J, Ibrić S, Đurić Z. Quality-by-design in pharmaceutical development. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:1-16.
doi:10.1016/B978-1-907568-27-5.50001-9 .

Đuriš, Jelena, Ibrić, Svetlana, Đurić, Zorica, "Quality-by-design in pharmaceutical development" in Computer-Aided Applications in Pharmaceutical Technology (2013):1-16,
https://doi.org/10.1016/B978-1-907568-27-5.50001-9 . .

TY  - CHAP
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2023
AB  - This chapter provides a basic theoretical background on chemometrics and chemometric methods for the analysis of multivariate data. Multivariate data analysis is essential for both product and process development and optimization. Depending on the problem studied, classification and/or regression multivariate methods are applied for data analysis. Different supervised and unsupervised methods for classification and regression are presented, followed by examples of their application in pharmaceutical technology. Some of the methods described include principal component analysis, various supervised classification methods, multiple linear regression, principal component regression, partial least squares regression, support vector machines, etc.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Chemometric methods application in pharmaceutical products processes analysis control
SP  - 57
EP  - 90
DO  - 10.1016/B978-1-907568-27-5.50004-4
ER  - 

@inbook{
author = "Đuriš, Jelena and Ibrić, Svetlana and Đurić, Zorica",
year = "2013",
abstract = "This chapter provides a basic theoretical background on chemometrics and chemometric methods for the analysis of multivariate data. Multivariate data analysis is essential for both product and process development and optimization. Depending on the problem studied, classification and/or regression multivariate methods are applied for data analysis. Different supervised and unsupervised methods for classification and regression are presented, followed by examples of their application in pharmaceutical technology. Some of the methods described include principal component analysis, various supervised classification methods, multiple linear regression, principal component regression, partial least squares regression, support vector machines, etc.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Chemometric methods application in pharmaceutical products processes analysis control",
pages = "57-90",
doi = "10.1016/B978-1-907568-27-5.50004-4"
}

Đuriš, J., Ibrić, S.,& Đurić, Z.. (2013). Chemometric methods application in pharmaceutical products processes analysis control. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 57-90.
https://doi.org/10.1016/B978-1-907568-27-5.50004-4

Đuriš J, Ibrić S, Đurić Z. Chemometric methods application in pharmaceutical products processes analysis control. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:57-90.
doi:10.1016/B978-1-907568-27-5.50004-4 .

Đuriš, Jelena, Ibrić, Svetlana, Đurić, Zorica, "Chemometric methods application in pharmaceutical products processes analysis control" in Computer-Aided Applications in Pharmaceutical Technology (2013):57-90,
https://doi.org/10.1016/B978-1-907568-27-5.50004-4 . .

TY  - CHAP
AU  - Đuriš, Jelena
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2021
AB  - This chapter provides a basic theoretical background on experimental design application and interpretation. Techniques described include screening designs, full and fractional factorial designs, Plackett-Burman design, D-optimal designs, response surface methodology, central composite designs, Box-Behnken design, and mixture designs, etc. The reader will be introduced to the experimental domains covered by specific design, making it easier to select the one appropriate for the problem. After theoretical introduction, a number of illustrative examples of design of experiments application in the field of pharmaceutical technology are presented.
PB  - Elsevier Inc.
T2  - Computer-Aided Applications in Pharmaceutical Technology
T1  - Experimental design application interpretation in pharmaceutical technology
SP  - 31
EP  - 56
DO  - 10.1016/B978-1-907568-27-5.50003-2
ER  - 

@inbook{
author = "Đuriš, Jelena and Ibrić, Svetlana and Đurić, Zorica",
year = "2013",
abstract = "This chapter provides a basic theoretical background on experimental design application and interpretation. Techniques described include screening designs, full and fractional factorial designs, Plackett-Burman design, D-optimal designs, response surface methodology, central composite designs, Box-Behnken design, and mixture designs, etc. The reader will be introduced to the experimental domains covered by specific design, making it easier to select the one appropriate for the problem. After theoretical introduction, a number of illustrative examples of design of experiments application in the field of pharmaceutical technology are presented.",
publisher = "Elsevier Inc.",
journal = "Computer-Aided Applications in Pharmaceutical Technology",
booktitle = "Experimental design application interpretation in pharmaceutical technology",
pages = "31-56",
doi = "10.1016/B978-1-907568-27-5.50003-2"
}

Đuriš, J., Ibrić, S.,& Đurić, Z.. (2013). Experimental design application interpretation in pharmaceutical technology. in Computer-Aided Applications in Pharmaceutical Technology
Elsevier Inc.., 31-56.
https://doi.org/10.1016/B978-1-907568-27-5.50003-2

Đuriš J, Ibrić S, Đurić Z. Experimental design application interpretation in pharmaceutical technology. in Computer-Aided Applications in Pharmaceutical Technology. 2013;:31-56.
doi:10.1016/B978-1-907568-27-5.50003-2 .

Đuriš, Jelena, Ibrić, Svetlana, Đurić, Zorica, "Experimental design application interpretation in pharmaceutical technology" in Computer-Aided Applications in Pharmaceutical Technology (2013):31-56,
https://doi.org/10.1016/B978-1-907568-27-5.50003-2 . .

TY  - JOUR
AU  - Đuriš, Jelena
AU  - Nikolakakis, Ioannis
AU  - Ibrić, Svetlana
AU  - Đurić, Zorica
AU  - Kachrimanis, Kyriakos
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1997
AB  - Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutics and Biopharmaceutics
T1  - Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting
VL  - 84
IS  - 1
SP  - 228
EP  - 237
DO  - 10.1016/j.ejpb.2012.12.018
ER  - 

@article{
author = "Đuriš, Jelena and Nikolakakis, Ioannis and Ibrić, Svetlana and Đurić, Zorica and Kachrimanis, Kyriakos",
year = "2013",
abstract = "Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic-polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus (R)) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential. scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus (R) was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus (R) is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed similar to 5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus (R) hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
title = "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting",
volume = "84",
number = "1",
pages = "228-237",
doi = "10.1016/j.ejpb.2012.12.018"
}

Đuriš, J., Nikolakakis, I., Ibrić, S., Đurić, Z.,& Kachrimanis, K.. (2013). Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics
Elsevier Science BV, Amsterdam., 84(1), 228-237.
https://doi.org/10.1016/j.ejpb.2012.12.018

Đuriš J, Nikolakakis I, Ibrić S, Đurić Z, Kachrimanis K. Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting. in European Journal of Pharmaceutics and Biopharmaceutics. 2013;84(1):228-237.
doi:10.1016/j.ejpb.2012.12.018 .

Đuriš, Jelena, Nikolakakis, Ioannis, Ibrić, Svetlana, Đurić, Zorica, Kachrimanis, Kyriakos, "Preparation of carbamazepine-Soluplus (R) solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting" in European Journal of Pharmaceutics and Biopharmaceutics, 84, no. 1 (2013):228-237,
https://doi.org/10.1016/j.ejpb.2012.12.018 . .

TY  - JOUR
AU  - Petrović, Jelena
AU  - Ibrić, Svetlana
AU  - Betz, Gabriele
AU  - Đurić, Zorica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1705
AB  - The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees
VL  - 428
IS  - 1-2
SP  - 57
EP  - 67
DO  - 10.1016/j.ijpharm.2012.02.031
ER  - 

@article{
author = "Petrović, Jelena and Ibrić, Svetlana and Betz, Gabriele and Đurić, Zorica",
year = "2012",
abstract = "The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees",
volume = "428",
number = "1-2",
pages = "57-67",
doi = "10.1016/j.ijpharm.2012.02.031"
}

Petrović, J., Ibrić, S., Betz, G.,& Đurić, Z.. (2012). Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 428(1-2), 57-67.
https://doi.org/10.1016/j.ijpharm.2012.02.031

Petrović J, Ibrić S, Betz G, Đurić Z. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees. in International Journal of Pharmaceutics. 2012;428(1-2):57-67.
doi:10.1016/j.ijpharm.2012.02.031 .

Petrović, Jelena, Ibrić, Svetlana, Betz, Gabriele, Đurić, Zorica, "Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees" in International Journal of Pharmaceutics, 428, no. 1-2 (2012):57-67,
https://doi.org/10.1016/j.ijpharm.2012.02.031 . .

TY  - JOUR
AU  - Cvijić, Sandra
AU  - Parojčić, Jelena
AU  - Đurić, Zorica
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1779
AB  - The main prerequisite to establish quantitative in vitro-in vivo correlation (IVIVC) and define biorelevant in vitro methodology is to identify drug dissolution profile in vivo. When intravenous data are not available due to poor drug solubility, oral drug absorption cannot be estimated by means of conventional pharmacokinetic analysis. Development of the mechanistic absorption models has therefore received widespread attention over the past few years. The objective of this study is to: I) develop drug-specific absorption model for carbamazepine using in silico absorption model, II) use the generated absorption model to provide the target in vivo dissolution profile for IVIVC, III) identify biorelevant dissolution specifications for carbamazepine immediate-release tablets, and IV) compare the obtained results with the results of the previous studies. GastroPlusTM software package was used for computer simulations. The required input parameters were experimentally determined, in silico predicted and/or taken from the literature. Convolution approach was applied to assess the relationship between the in vitro and in vivo data. The presented data demonstrated that in silico simulation technology can be successfully used to predict carbamazepine absorption profile, and that the generated plasma concentration profile can serve as the target profile for IVIVC and identification of biorelevant dissolution specifications for carbamazepine immediate-release tablets.
AB  - Da bi se procenila mogućnost primene laboratorijskih (in vitro) i računarskih (in silico) metoda za predviđanje apsorpcije lekovite supstance u gastrointestinalnom traktu (GIT-u) i uspostavljanje in vitro-in vivo korelacije (IVIVK), neophodno je prethodno identifikovati in vivo profil oslobađanja lekovite supstance iz preparata. U slučaju lekovitih supstanci koje, zbog slabe rastvorljivosti, nije moguće primeniti intravenski, apsorpciju nije moguće predvideti primenom konvencionalnih farmakokinetičkih metoda, pa je zato poslednjih godina veliki istraživački interes usmeren ka primeni mehanističkih apsorpcionih modela. Cilj ovog rada je da se: i) primenom in silico apsorpcionog modela razvije lek-specifičan model za predviđanje apsorpcije karbamazepina, ii) identifikuje profil in vivo oslobađanja koji će služiti kao osnova za uspostavljanje IVIVK, iii) identifikuju biorelevantne specifikacije za brzinu rastvaranja karbamazepina iz tableta sa trenutnim oslobađanjem i iv) dobijeni rezultati uporede sa rezultatima prethodnih studija. Za in silico predviđanje apsorpcije karbamazepina primenjen je GastroPlusTM programski paket. Vrednosti ulaznih parametara potrebnih za simulaciju su preuzete iz literature ili su korišćene in silico predviđene i/ili eksperimentalno određene vrednosti. Za utvrđivanje stepena korelacije između in vitro i in vivo podataka primenjen je konvolucioni pristup uspostavljanju IVIVK. Dobijeni rezultati su pokazali da je primenom in silico metode moguće uspešno simulirati apsorpciju karbamazepina nakon oralne primene i da se dobijeni profil koncentracije leka u krvi može koristiti kao ciljni profil za IVIVK i identifikovanje 'biorelevantnih' specifikacija za in vitro brzinu rastvaranja karbamazepina iz tableta.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Mechanistic simulation of carbamazepine absorption after oral administration of immediate release tablets
T1  - In silico predviđanje apsorpcije karbamazepina nakon oralne primene tableta sa trenutnim oslobađanjem
VL  - 62
IS  - 3
SP  - 219
EP  - 236
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1779
ER  - 

@article{
author = "Cvijić, Sandra and Parojčić, Jelena and Đurić, Zorica",
year = "2012",
abstract = "The main prerequisite to establish quantitative in vitro-in vivo correlation (IVIVC) and define biorelevant in vitro methodology is to identify drug dissolution profile in vivo. When intravenous data are not available due to poor drug solubility, oral drug absorption cannot be estimated by means of conventional pharmacokinetic analysis. Development of the mechanistic absorption models has therefore received widespread attention over the past few years. The objective of this study is to: I) develop drug-specific absorption model for carbamazepine using in silico absorption model, II) use the generated absorption model to provide the target in vivo dissolution profile for IVIVC, III) identify biorelevant dissolution specifications for carbamazepine immediate-release tablets, and IV) compare the obtained results with the results of the previous studies. GastroPlusTM software package was used for computer simulations. The required input parameters were experimentally determined, in silico predicted and/or taken from the literature. Convolution approach was applied to assess the relationship between the in vitro and in vivo data. The presented data demonstrated that in silico simulation technology can be successfully used to predict carbamazepine absorption profile, and that the generated plasma concentration profile can serve as the target profile for IVIVC and identification of biorelevant dissolution specifications for carbamazepine immediate-release tablets., Da bi se procenila mogućnost primene laboratorijskih (in vitro) i računarskih (in silico) metoda za predviđanje apsorpcije lekovite supstance u gastrointestinalnom traktu (GIT-u) i uspostavljanje in vitro-in vivo korelacije (IVIVK), neophodno je prethodno identifikovati in vivo profil oslobađanja lekovite supstance iz preparata. U slučaju lekovitih supstanci koje, zbog slabe rastvorljivosti, nije moguće primeniti intravenski, apsorpciju nije moguće predvideti primenom konvencionalnih farmakokinetičkih metoda, pa je zato poslednjih godina veliki istraživački interes usmeren ka primeni mehanističkih apsorpcionih modela. Cilj ovog rada je da se: i) primenom in silico apsorpcionog modela razvije lek-specifičan model za predviđanje apsorpcije karbamazepina, ii) identifikuje profil in vivo oslobađanja koji će služiti kao osnova za uspostavljanje IVIVK, iii) identifikuju biorelevantne specifikacije za brzinu rastvaranja karbamazepina iz tableta sa trenutnim oslobađanjem i iv) dobijeni rezultati uporede sa rezultatima prethodnih studija. Za in silico predviđanje apsorpcije karbamazepina primenjen je GastroPlusTM programski paket. Vrednosti ulaznih parametara potrebnih za simulaciju su preuzete iz literature ili su korišćene in silico predviđene i/ili eksperimentalno određene vrednosti. Za utvrđivanje stepena korelacije između in vitro i in vivo podataka primenjen je konvolucioni pristup uspostavljanju IVIVK. Dobijeni rezultati su pokazali da je primenom in silico metode moguće uspešno simulirati apsorpciju karbamazepina nakon oralne primene i da se dobijeni profil koncentracije leka u krvi može koristiti kao ciljni profil za IVIVK i identifikovanje 'biorelevantnih' specifikacija za in vitro brzinu rastvaranja karbamazepina iz tableta.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Mechanistic simulation of carbamazepine absorption after oral administration of immediate release tablets, In silico predviđanje apsorpcije karbamazepina nakon oralne primene tableta sa trenutnim oslobađanjem",
volume = "62",
number = "3",
pages = "219-236",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1779"
}

Cvijić, S., Parojčić, J.,& Đurić, Z.. (2012). Mechanistic simulation of carbamazepine absorption after oral administration of immediate release tablets. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 62(3), 219-236.
https://hdl.handle.net/21.15107/rcub_farfar_1779

Cvijić S, Parojčić J, Đurić Z. Mechanistic simulation of carbamazepine absorption after oral administration of immediate release tablets. in Arhiv za farmaciju. 2012;62(3):219-236.
https://hdl.handle.net/21.15107/rcub_farfar_1779 .

Cvijić, Sandra, Parojčić, Jelena, Đurić, Zorica, "Mechanistic simulation of carbamazepine absorption after oral administration of immediate release tablets" in Arhiv za farmaciju, 62, no. 3 (2012):219-236,
https://hdl.handle.net/21.15107/rcub_farfar_1779 .