Development and Biopharmaceutical Characterization of BCS Class II Drug ?Naproxen by Two Way Complexation Solid Dispersion Technique

Abstract

Author(s): Milind DharmrajKamble, Zahid Zaheer, Rana Zainuddin, Santosh Mokale

The objective of this study was to increase the solubility and bioavailability of Naproxen (NP) by fabricating ternary solid dispersion (tSDs) with water soluble polymer PEG 6000 and crospovidone. tSDs were prepared and optimized by 32full factorial design with PEG 6000 level (X1) and CP level (X2) as independent variables and percent drug release (D80, (Y)) as dependent variable. The optimized tSDs were evaluated for their physicochemical properties which confirmed the formation of tSDs (DSC), SEM suggested smooth surface and compact structures. PXRD revels that drug was still present in crystalline form and was not molecularly dispersed in the complex especially in non-homogeneous part of the tSDs. The optimized tSDs revels that Dissolution rate (Y) was significantly affected by independent variable PEG 6000 (X1) while CP (X2) was insignificant. The transparent characteristics of tSDs was observed as a result of lowered Tg temperature gives higher dissolution rate up to 97.70 % for optimized formulation (F9). The pharmacokinetic study in Han Wistar rats showed that the tSDs had the greatest effect on oral bioavailability of NP in vivotest showed that NP (tSDs) presented significantly larger AUC0-t, which was 1.09 folds more than that of marketed formulation. Cmaxof NP (tSDs) also increased from 120 μg/ml to 146 μg/ml compared to that of marketed formulations and generated shortened Tmaxof (1.0 ± 0.416) h, compared to marketed dosage form(2.0 ± 0.456) h