Improved solubility and bioavailability of practically insoluble sildenafil base for the treatment of erectile dysfunction

Abstract

The aim of this research was to compare the solubility, dissolution, physicochemical properties and oral bioavailability of various solubility-enhancing techniques to select the best drug delivery system with the highest oral bioavailability of practically insoluble sildenafil base. The liquid self-nanoemulsifying drug delivery system (liquid SNEDDS) was composed of sildenafil base/Labrasol/Transcutol/coconut oil at the ratio of 10/0.72/0.18/0.1 (w/v/v/v). SPG membrane emulsification or high pressure homogenizer were used for emulsion droplet size reduction and homogenization of liquid SNEDDS. The solid SNEDDS was prepared with the optimized liquid SNEDDS and inert carriers (silicon dioxide). The solvent-evaporated solid dispersion (SE) and the surface-attached solid dispersion (SA) were prepared with sildenafil base/PVP/Labrasol at the optimized ratio of 1/6/1 (w/w/w) using ethanol and distilled water, respectively. All solid state products were achieved by the spray-drying technique. Their physicochemical properties were examined by the SEM, DSC, PXRD and particle size analyser. Moreover, their aqueous solubility, dissolution and pharmacokinetics in rats were performed in comparison with the sildenafil base powder. All the formulations significantly improved the solubility, dissolution and oral bioavailability of sildenafil base as compared to the drug powder due to reduced particle size and conversion to the amorphous state. In particular, solvent-evaporated solid dispersion technique showed the highest solubility, dissolution and oral bioavailability among all techniques. Accordingly, solvent-evaporated solid dispersion could be potential drug delivery system for oral administration of practically insoluble sildenafil base with remarkably improved bioavailability.