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Dissolution Rate Enhancement and Physicochemical Characterization of Carbamazepine-Poloxamer Solid Dispersions

Dissolution Rate Enhancement and Physicochemical Characterization of Carbamazepine-Poloxamer Solid Dispersions

Djordje P Medarević, Kyriakos Kachrimanis, Miodrag Mitrić, Jelena Djuriš, Zorica Djurić, Svetlana Ibrić

Pharm Dev Technol. 2016;21(3):268-76.

PMID: 25582577

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP9003116-C	Poloxamer solid		9003-11-6	Price

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