Improvement of simvastatin dissolution rate using derivative non-covalent approach by solvent drop grinding method

Abstract

Objective: This study aimed to enhance the solubility of simvastatin using noncovalent derivatives (NCDs) with oxalic acid (OA), fumaric acid (AF), and nicotinamide (NK) as conformers. Methods: NCDs were prepared using by a solvent drop grinding (SDG). The NCDs formed were evaluated for saturated solubility test, NCDs with the highest saturation solubility were then characterized by Fourier transform infrared spectrophotometry (FT-IR), differential scanning calorimeter (DSC), powder x-ray diffractometry (PXRD) and the particulate dissolution using type II of USP test. Results: SV-OA NCDs showed the highest solubility; thus NCDS of SV-OA were characterized by X-ray diffraction showing a new peak at 2ϴ = 28.96 °C and differential scanning calorimeter showed a change of endothermic peak from 134.3 °C to 69 °C. Infrared spectroscopy indicated that there were no functional group changes from simvastatin, while the dissolution rate increased from 68.22% to 76.08%. Conclusion: SV-OA NCDs show an increased profile of solubility and dissolution compared to pure simvastatin.