Preparation, characterization and pharmacodynamic evaluation of fused dispersions of simvastatin using PEO-PPO block copolymer

ABSTRACT

The solubility enhancement of poorly soluble compounds is an important task in pharmaceutical technology as it leads to better bioavailability and a more efficient application. Fused dispersions [FDs] of simvastatin [SIM] using PEO-PPO block copolymer were prepared which paved the way for the formation of an amorphous product with enhanced dissolution and bioavailability. The accumulative solubility of simvastatin [SIM] from PEO-PPO block copolymer [Lutrol NF 127 prill surfactant] was found to be superior to the drug alone which may be due to the increased oxyethylene content that played the major role in solubility enhancement. A 3[2] full factorial approach was used for optimization wherein the temperature to which the melt-drug mixture cooled [X[1]] and the drug-to-polymer ratio [X[2]] were selected as the independent variables and the time required for 90% drug dissolution [t[90%]] was selected as the dependent variable. A low level of X[1] and a high level of X[2] were suitable for obtaining higher dissolution of SIM from SIM FDs. On increasing melt to cool drug temperature, t[90%] increased thus improving dissolution rate of FD[2] batch with the maximum drug release [99.63%] in 120 min. The optimized FDs were characterized by saturation solubility study, drug content, in-vitro dissolution, fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, x-ray diffraction, [1]HNMR spectroscopy and pharmacodynamic evaluation. Capsules containing optimized FDs were prepared and compared with marketed brand [SIMVOTIN[registered]]. Finally, it can be concluded that the optimized FDs of SIM ameliorate the solubility and dissolution of drug with improved pharmacodynamic activity