The aim of present investigation is to enhance the solubility and dissolution behaviour of poorly soluble drug simvastatin. The simvastatin-phospholipid complex (SPC) was prepared using a modified solvent evaporation method. A circumscribed central composite design was used to analyze, and optimize the formulation and the process variables to obtain acceptable simvastatin-phospholipid complex (SPC). The influence of phospholipid-to-drug ratio (X1, w: w), reaction temperature (X,"C) and the reaction time (X, h) on the entrapment efficiency of simvastatin in SPC were evaluated. The prepared SPC was then characterized by Fourier Transformed Infrared (FTIR) Spectroscopy, Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). Additionally, the SPC was evaluated for apparent aqueous solubility, and in-vitro release of simvastatin. The optimum conditions identified to obtain a high efficiency SPC were, phospholipid-to-drug ratio of 3:1, the reaction temperature of 60°C, and a reaction time of 3 hours. The SEM images indicated that SPC was composed of irregular size vesicles of hydrogenated soy phosphatidylcholine, and simvastatin intercalated in the lipid layers. The results showed that formulation of SPC significantly increased the aqueous solubility of simvastatin. Additionally, the in-vitro dissolution results showed that, at the end of 8 hours, free simvastatin showed about 16% release; whereas, the drug release from SPC was over 98%. This increase in solubility and the dissolution characteristics of the complex may be explained by the amphiphilic nature of the complex, as well as possible amorphization of the drug by the phospholipid. The prepared SPC showed a significant (27 fold) enhancement in the apparent aqueous solubility, as well as the dissolution behavior of simvastatin. Drug-phospholipid complexes can serve as a potential alternative strategy for enhancing the aqueous solubility of poorly water soluble drugs such as simvastatin.
Cite this article:
Saoji, Rode, Saoji and Belgamwar (2016). Solubility and Dissolution Rate Improvement of Simvastatin via Phospholipid Complexation. Journal of Ravishankar University (Part-B: Science), 29(1), pp.146-147.