Dissolution Improvement of Simvastatin by Surface Solid Dispersion Technology

Abstract

The objective of the present study was to formulate surface solid dispersions (SSD) of simvastatin to improve the aqueous solubility and dissolution rate to facilitate faster onset of action. Simvastatin is a BCS Class II drug having low solubility (1.45 g/mL) and therefore low oral bioavailability (5%). In the present study, SSDs of simvastatin with two different superdisintegrants in three different drug-carrier ratios were prepared by a coevaporation method. Surface solid dispersions were characterized by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and infrared spectroscopy (IR) and evaluated for drug content, saturation solubility, pH-dependent solubility, solubility in biorelevant media (i.e., fasted-state simulated intestinal fluid [FaSSIF] and fed-state simulated intestinal fluid [FeSSIF]), in vitro dissolution, and in vivo studies by a Triton-induced hypercholestermia model in rats. DSC studies revealed that there was no interaction between drug and carrier, whereas the PXRD study demonstrated that there was a significant decrease in crystallinity of pure drug present in surface solid dispersions, which resulted in an increased dissolution rate of simvastatin.