Rosuvastatin-loaded solid SMEDDS: an innovative approach for solubility augmentation and improved pharmacodynamic profile

Abstract

The objectives undertaken in current work were to develop a new solid self-microemulsifying drug delivery system (S-SMEDDS) for poorly water-soluble Rosuvastatin Calcium (RST) and evaluate its antihyperlipidemic activity in rodent model. Solubility assessment in variety of excipients, screening studies and optimization of pseudoternary plots helped in development of liquid SMEDDS. Liquid SMEDDS of RST contained Capryol 90, Kolliphor EL and Transcutol HP as oil phase, surfactant and co-surfactant respectively which were evaluated for release, self-emulsification ability, percentage transmittance and globule size. Florite RE was used as the adsorbent to transform the optimized liquid SMEDDS into non-coherent powder which was then examined for micromeritic properties, solid state characterization and in vitro dissolution studies. It was additionally investigated for antihyperlipidemic activity in rats subjected to high fat diet. Optimized liquid SMEDDS of RST was found to undergo a swift transformation in a microemulsion having globule size in nanometric size range with consistent size distribution. The liquid SMEDDS adsorbed on Florite RE exhibited favorable micromeritic properties and spherical shape. XRD studies indicated amorphization of RST due to its molecular dispersion in S-SMEDDS. Enhanced in vitro rate of dissolution of optimized formulation was observed in comparison to pure drug and commercial product. There was considerable reduction (p < 0.001) in serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C), very low-density lipoproteins (VLDL-C) when S-SMEDDS was administered and increment in high-density lipoproteins (HDL-C) level compared to plain drug suspension. RST S-SMEDDS holds great potential for enhancement of its physiochemical along with biological attributes.