Abstract

Poor oral bioavailability of BCS class 4 drug is due to poor aqueous solubility and poor permeability across intestine. Present work was undertaken to increase oral bioavailability of BCS class 4 drug i.e. Cefixime using P-glycoprotein inhibitor hydrophile i.e. Pluronic and complexing agent beta cyclodextrin.

Comparative study was carried out using Pluronic as solid dispersion and beta cyclodextrin as inclusion complexation in different drug to polymer ratios through physical mix, kneading, solvent evaporation and spray drying technique. Physicochemical characterisation was done using saturated solubility studies, in vitro dissolution, ATR, DSC, SEM, and XRD study.

Prepared formulations were also evaluated for % drug permeation using non-everted rat intestinal sac method which showed that Pluronic was not involved in permeability enhancement of Cefixime.

Solid dispersion prepared with Pluronic found to show marked increment in solubility and dissolution as well as in ex-vivo permeation study.

In vivo study was carried out using Pluronic sd in male Wister rats (n=6) and which showed enhanced absorption of Cefixime with AUC 1.9 times greater than of the aqueous plain Cefixime suspension. Thus, BCS class 4 Cefixime can be treated as bcs class 2 by increasing its solubility instead of permeability as evident by ex-vivo and in vivo study.

Keywords: Cefixime; Pluronic; Cyclodextrin; Permeability; Solubility; Dissolution