The Effect of PEG Molecular Weights on Dissolution Behavior of Simvastatin in Solid Dispersions

The purpose of the present study was to investigate the effect of polyethylene glycol (PEG) molecular weights (6000, 12000 and 20000) as solid dispersion (SD) carriers on the dissolution behavior of simvastatin. SDs with various drug: carrier ratios were prepared by solvent method and evaluated for dissolution rate. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), infrared spectroscopy and solubility studies were also performed on the optimum SD formulation. Samples prepared with all three types of PEG showed improved drug dissolution compared to intact drug and corresponding physical mixtures. Meanwhile, the best result was obtained by PEG 12000 with drug: carrier ratio of 1:7 which showed a 3-fold increase in dissolution rate compared to the intact drug. Based on DSC and XRD, no crystalline change occurred during the sample preparation. Solubility studies revealed that increasing the PEG molecular weight resulted in higher phase solubility of drug. In addition, saturated solubility of the optimum SD was significantly higher than that of intact drug and the related physical mixture (24.83, 8.74 and 8.88 μg/mL, respectively) that could be due to the decreased particle size and aggregation. The results confirmed the influence of PEG molecular weight on drug dissolution rate from solid dispersion systems.