Characterization of Solid Dispersions of Simvastatin with PVP K30 and Poloxamer 188

Abstract:

The present study involved preparation of solid dispersions of simvastatin to improve the aqueous solubility and dissolution rate in order to facilliatate faster onset of action. simvastatin is a BCS class II durg having low aqueos solubility [1.45ug/ml] and therefore low oral bioavailability [5%]. in the present study,solid dispersions of simvastatin with two different carriers in three different drugs: carier rations were prepared by spray drying method. Solid dispersions were characterized by differential scanning calorimetry, powder x-ray diffractometry, scanning electron microscopy and infrared spectroscopy and evaluated for drug content, saturation solubality stueies colubality in biorelevant media i.e fasting state simulated intestinal fluid and fed state simulated intestinal fluid and fed state simulated intestinal fluid , in vitro dissolution and pharmacodynamic studies by triton induced hypercholestermia models in rats. saturation solubility with PVP K30 dispersion [1:3] and poloxamer 188[1:3] was found to increase by 617.59% and 1028.04% respectively as compared to plain drug. solubility in biorelevant media was also found to be significantly drug in 60 min. Xray diffraction spectra revealed a significant decrease in crystallinity of drug in solid dispersions which resulted in increased dissolution rate of simvastatin. The in virto results were corroborated by the pharmacodynamic studies in rate. In conclusion, solid dispersions of simvastatin with poloxamer 188 showed superior solubillity enhancement as compared to that with PVPK30.

KEY WORDS: solid dispersion, Biorelevant Media FASSIF, FeSS, Simvastatin.