Enhancement of Solubility and Bioavailability of Etravirine Solid Dispersions by Solvent Evaporation Technique with Novel Carriers

Abstract

Among the different solubility enhancement techniques, solid dispersion is the most efficient technique in improving the solubility and rate of in-vitro / and in-vivo dissolution of poorly soluble drug substance (s). Etravirine is a new non-nucleoside reverse transcriptase inhibitor of human immune deficiency virus type 1, which is belongs to BCS class IV molecule. In the present study, immediate release solid dispersion of antiretroviral Etravirine was formulated by solvent evaporation technique. Twelve solid dispersions were prepared with 1:1:1 and 1:2:1 ratios of drug: carrier: surfactant. There was significant improvement in the rate of drug release from all 12 solid dispersions and found to be comparable to the dissolution profiles of Innovator product (Intelence ® 200 mg Tablets). The solid dispersion formulation (SE6) comprising Etravirine: Kolliphor P407: surfactant (1:2:1) by solvent evaporation process has shown enhanced solubility about 9 folds and significant improvement in rate of drug release. Polymorphic form of Etravirine has been converted into an amorphous form from crystalline within the solid dispersion formulation. Formulation (SE6) has shown marked increase in rate of dissolution and bioavailability. AUC0-inf was increased by 2.1 folds, Cmax increased by 2.3 folds and tmax reduced by 1 hr as compared to the Etravirine.