PREPARATION, CHARACTERIZATION AND DISSOLUTION OF SOLVENT EVAPORATED SIMVASTATIN SOLID DISPERSIONS

Abstract

Simvastatin an antihyperlipidemic BCS class II drug, suffering from poor water solubility. This problem may affect the bioavailability as well as pharmacological action of the drug. To overcome this solubility issue, solid dispersions of simvastatin were prepared and compared with marketed formulation “SIMVOTIN 20” in this study. Solid dispersions of simvastatin were prepared by using the solvent evaporation method. Solid dispersions of simvastatin with PVP K90 (1:1-1:5), HPMC E50 (1:1-1:5), and Poloxamer 450 (1:1 to 1:3) with and without 1% Sodium lauryl sulfate were prepared by a solvent evaporation method. The characterization studies such as Fourier transform infra-red (FTIR), differential scanning calorimetry (DSC), Hot stage microscopy (HSM), powdered X-ray crystallographic studies (PXRD) were performed to evaluate physiochemical change in the optimized formulation. The dissolution test showed the enhancement of dissolution as compared to the pure drug, physical mixture and marketed formulation “SIMVOTIN 20” in all three types of formulation, but formulation containing ratio 1:3:1 (simvastatin: Poloxamer: 1% SLS) showed the faster drug release as compared to other formulations. The Fourier transform infra-red (FTIR) study showed no interaction between the drug and polymers. The differential scanning colorimetry (DSC) and hot stage Microscopy (HSM) showed change in nature of the drug further verified by powdered X-ray crystallographic studies (PXRD) study. These studies showed the amorphous nature of the formulation may be a reason for enhancement of dissolution rate. Hence solid dispersion formulation may be an effective approach for solubility enhancement of a BCS Class II drug.