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  - Kovacević, Jovana
AU  - Ibrić, Svetlana
AU  - Đuriš, Jelena
AU  - Kleinebudde, Peter
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2543
AB  - This study consists of two experimental designs. Within the first one, suitable technique for application of model drug onto inactive pellets was evaluated and formulation and process parameters with greatest impact to process efficency and useful yield were determined. Results of experiments showed that formulation characteristics were the ones with the greatest impact on coating efficiency and that suspension layering technique was significantly better for drug application onto inactive pellets in comparison to solution layering during which pronounced agglomeration of pellets occurred. Analysis of drug-polymer interactions by differential scanning calorimetry was performed to explain the results of experiments. The reason for agglomeration of pellets during solution layering was formation of low Tg amorphous form of model drug. The second set of experiments was performed according to central composite design experimental plan in order to optimize level of binder and concentration of solids in the coating liquid which were found to have greatest positive impact on process efficiency and useful yield in the screening study. Statistically significant models were obtained by response surface methodology and it was possible to use them to define optimal levels of excipients in the formulation.
PB  - Elsevier Science BV, Amsterdam
T2  - International Journal of Pharmaceutics
T1  - Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions
VL  - 506
IS  - 1-2
SP  - 312
EP  - 319
DO  - 10.1016/j.ijpharm.2016.04.030
ER  - 

@article{
author = "Kovacević, Jovana and Ibrić, Svetlana and Đuriš, Jelena and Kleinebudde, Peter",
year = "2016",
abstract = "This study consists of two experimental designs. Within the first one, suitable technique for application of model drug onto inactive pellets was evaluated and formulation and process parameters with greatest impact to process efficency and useful yield were determined. Results of experiments showed that formulation characteristics were the ones with the greatest impact on coating efficiency and that suspension layering technique was significantly better for drug application onto inactive pellets in comparison to solution layering during which pronounced agglomeration of pellets occurred. Analysis of drug-polymer interactions by differential scanning calorimetry was performed to explain the results of experiments. The reason for agglomeration of pellets during solution layering was formation of low Tg amorphous form of model drug. The second set of experiments was performed according to central composite design experimental plan in order to optimize level of binder and concentration of solids in the coating liquid which were found to have greatest positive impact on process efficiency and useful yield in the screening study. Statistically significant models were obtained by response surface methodology and it was possible to use them to define optimal levels of excipients in the formulation.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "International Journal of Pharmaceutics",
title = "Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions",
volume = "506",
number = "1-2",
pages = "312-319",
doi = "10.1016/j.ijpharm.2016.04.030"
}

Kovacević, J., Ibrić, S., Đuriš, J.,& Kleinebudde, P.. (2016). Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 506(1-2), 312-319.
https://doi.org/10.1016/j.ijpharm.2016.04.030

Kovacević J, Ibrić S, Đuriš J, Kleinebudde P. Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions. in International Journal of Pharmaceutics. 2016;506(1-2):312-319.
doi:10.1016/j.ijpharm.2016.04.030 .

Kovacević, Jovana, Ibrić, Svetlana, Đuriš, Jelena, Kleinebudde, Peter, "Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions" in International Journal of Pharmaceutics, 506, no. 1-2 (2016):312-319,
https://doi.org/10.1016/j.ijpharm.2016.04.030 . .