Enhanced Dissolution Profile and Antihyperlipedimic Activity of Simvastatin by Solid Dispersion with Pluronic F68

Background and Purpose of Study: Simvastatin (SIM) is a 3-hydroxy-3methylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor that is insoluble in water. Its low water solubility rate limits the pharmacological effects. Pluronic F68, a hydrophilic polymer is known for its hepatic CYP3A4 enzyme inhibition. CYP3A4 is the key enzyme for the metabolism of SIM in liver. The aim of the present study was to improve solubility, dissolution rate and antihyperlipedimic activity of SIM using solid dispersion with pluronic F68. Methods: The solid dispersions in different w/v ratio were prepared by solvent evaporation method. The solid dispersions were evaluated for drug content, saturation solubility, in vitro dissolution rate and for their in vivo antihyperlipedimic activity. The probable drug polymer interactions were studied by fourier transform infrared (FTIR) spectroscopy. Results and Major Conclusions: Probable machanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC) and Powder X-ray diffractomery (PXRD) of drug and solid dispersions. This study revealed that preparation of solid dispersion of SIM with pluronic F68 is not only improving the dissolution of SIM but also enhancing its antihyperlipedimic activity.