TY  - JOUR
AU  - Krstić, Marko
AU  - Lukić, I
AU  - Bušatlić, A
AU  - Lazarević, N
AU  - Vasiljević, Dragana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3130
AB  - Solid dispersions are defined as dispersions of one or more active pharmaceutical ingredients in inert solid-state carriers. They are made with the aim to increase solubility and the dissolution rate of low solubility active pharmaceutical ingredients, with the subsequent increase in their bioavailability. The aim of this study was the development and optimization of solid dispersion formulations with carbamazepine, using D-optimal experimental design, in order to increase the dissolution rate of the selected model drug. By using the method of experimental mixture design, solid dispersions were formulated by varying the ratio of carbamazepine (30-50 %), Gelucire® 44/14 (20-40 %) and Soluplus® polymer (30-50 %) (input parameters). Sixteen formulations were made and used for in vitro testing of the carbamazepine dissolution rate. The observed output parameters were the percentages of carbamazepine released after 10, 20, 30, 45, and 60 minutes. After the data analysis, three test formulations were chosen from different parts of the optimization area. They were prepared and the carbamazepine dissolution rate was determined, followed by stability assessment for 24 months under ambient conditions (25 °C, 40 % RH). The highest dissolution rate of carbamazepine from solid dispersions (more than 80 % in 30 minutes) was achieved at the carbamazepine mass fraction of about 40 %, Soluplus® of about 45 % and Gelucire® 44/14 of about 25 %. Comparing the predicted and the experimental obtained release rate profiles of carbamazepine from the three prepared optimized formulations, a significant compliance of the results was observed (f1<15; f2 >50). The application of the PAMPA (Parallel Artificial-Membrane Permeability Assay) test has shown that carbamazepine premeability was maintained and mildly increased in two out of the three tested optimzed solid state formulations. Raman spectroscopy, FT-IR and DSC analyes showed that in the three optimized solid dispersions, after preparation and 24 months of storage, interactions between carbamazepine and the excipients were not present and that carbamazepine remained in the single pharmacologically active crystal polymorph form III. Proper selection of solid dispersion proportions of carbamazepine, Gelucire® 44/14 and Soluplus® may significantly increase the dissolution rate of the active substance, and the method of experimental mixture design can be successfully used for optimization of these formulations.
PB  - Savez hemijskih inženjera, Beograd
T2  - Hemijska industrija
T1  - Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability
T1  - Čvrste disperzije sa karbamazepinom: Optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti
VL  - 72
IS  - 4
SP  - 191
EP  - 204
DO  - 10.2298/HEMIND171025013K
ER  - 

@article{
author = "Krstić, Marko and Lukić, I and Bušatlić, A and Lazarević, N and Vasiljević, Dragana",
year = "2018",
abstract = "Solid dispersions are defined as dispersions of one or more active pharmaceutical ingredients in inert solid-state carriers. They are made with the aim to increase solubility and the dissolution rate of low solubility active pharmaceutical ingredients, with the subsequent increase in their bioavailability. The aim of this study was the development and optimization of solid dispersion formulations with carbamazepine, using D-optimal experimental design, in order to increase the dissolution rate of the selected model drug. By using the method of experimental mixture design, solid dispersions were formulated by varying the ratio of carbamazepine (30-50 %), Gelucire® 44/14 (20-40 %) and Soluplus® polymer (30-50 %) (input parameters). Sixteen formulations were made and used for in vitro testing of the carbamazepine dissolution rate. The observed output parameters were the percentages of carbamazepine released after 10, 20, 30, 45, and 60 minutes. After the data analysis, three test formulations were chosen from different parts of the optimization area. They were prepared and the carbamazepine dissolution rate was determined, followed by stability assessment for 24 months under ambient conditions (25 °C, 40 % RH). The highest dissolution rate of carbamazepine from solid dispersions (more than 80 % in 30 minutes) was achieved at the carbamazepine mass fraction of about 40 %, Soluplus® of about 45 % and Gelucire® 44/14 of about 25 %. Comparing the predicted and the experimental obtained release rate profiles of carbamazepine from the three prepared optimized formulations, a significant compliance of the results was observed (f1<15; f2 >50). The application of the PAMPA (Parallel Artificial-Membrane Permeability Assay) test has shown that carbamazepine premeability was maintained and mildly increased in two out of the three tested optimzed solid state formulations. Raman spectroscopy, FT-IR and DSC analyes showed that in the three optimized solid dispersions, after preparation and 24 months of storage, interactions between carbamazepine and the excipients were not present and that carbamazepine remained in the single pharmacologically active crystal polymorph form III. Proper selection of solid dispersion proportions of carbamazepine, Gelucire® 44/14 and Soluplus® may significantly increase the dissolution rate of the active substance, and the method of experimental mixture design can be successfully used for optimization of these formulations.",
publisher = "Savez hemijskih inženjera, Beograd",
journal = "Hemijska industrija",
title = "Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability, Čvrste disperzije sa karbamazepinom: Optimizacija formulacija, karakterizacija i ispitivanje dugoročne stabilnosti",
volume = "72",
number = "4",
pages = "191-204",
doi = "10.2298/HEMIND171025013K"
}

Krstić, M., Lukić, I., Bušatlić, A., Lazarević, N.,& Vasiljević, D.. (2018). Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability. in Hemijska industrija
Savez hemijskih inženjera, Beograd., 72(4), 191-204.
https://doi.org/10.2298/HEMIND171025013K

Krstić M, Lukić I, Bušatlić A, Lazarević N, Vasiljević D. Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability. in Hemijska industrija. 2018;72(4):191-204.
doi:10.2298/HEMIND171025013K .

Krstić, Marko, Lukić, I, Bušatlić, A, Lazarević, N, Vasiljević, Dragana, "Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability" in Hemijska industrija, 72, no. 4 (2018):191-204,
https://doi.org/10.2298/HEMIND171025013K . .