Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions.

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.

Combined application of mixture experimental design and artificial neural networks in the solid dispersion development.

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®-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®-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 (Q10) and 20 (Q20) 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.