Enhancement of Carvedilol Dissolution; Surface Solid Dispersion Versus Solid Dispersion

Abstract

The aim of this work was to improve the aqueous solubility of carvedilol (CRV), poorly water soluble drug, using surface solid dispersion (SSD) technique. Drug was deposited over the surface of a hydrophilic, water-insoluble carrier (Avicel pH 101) by solvent evaporation. Pluronic F68 was added as a wetting agent to some formulations. To estimate the effect of SSD technique on drug dissolution, solid dispersions (SDs) of dug and Pluronic F68 were prepared by solvent evaporation. Pluronic F68 was selected due to its inhibiting effect to CYP3A4, an enzyme that contribute to hepatic metabolism of CRV. All formulations were characterized by in vitro dissolution studies; X-ray powder diffraction and scanning electron microscopy. SSD enhanced drug dissolution compared to pure drug. The addition of polymer to drug/carrier composite greatly improved drug dissolution compared to that without the polymer. Compared to SD, SSD showed a better drug release rate. X-ray diffraction indicated the complete reduction in drug crystallinity and the formation of the amorphous form in case of SSD, with limited reduction in crystallinity for SD. The obtained dissolution efficiency of SSD was comparable to that obtained from the marketed CRV product. The study thus presented a system capable of increasing the dissolution rate of CRV with a potential for increased oral bioavailability by inhibiting its pre-systemic metabolism as well.