Preparation And Assessment Of Simvastatin SMEDDS Soft Capsules

Simvastatin which has been used as an inhibitor of HMG-COA deoxidization enzyme. Nowadays, the preparations of simvastatin have capsules, tablets, and film coated tablets etc. Due to its poor water solubility and absorption after oral administration, low bioavailability limits its clinical therapeutic effect.The SMEDDS can improve the absorption and bioavailability of poorly soluble drugs. In recently, much attention has been paid to this study. Therefore, SMEDDS is selected as the carrier to increase the absorption, dissolution and bioavailability of simvastatin.The HPLC method is developed for the assay and the gradient elution method is established for the related substances of SV-SMEDDS soft-capsules. After the methodological validation, the method established is accurate, reliable, stable and applicable to the quality control of the product in vitro.The compositions of SV-SMEDDS were selected by solubility assay, transmittance, pseudo-ternary phase diagrams analysis. The SMEDDS formulation was optimized using CCD-RSM. The optimal formulation was SV (5%), MCT (22%), Cremophor EL (51%), Labrasol (22%). The average particle diameter of microemulsion was57nm. Based on the time, size and morphology after self-micoremulsification, content, dissolution and stability studies, we evaluated the quality of SV-SMEDDS.Based on the viscosity of the gelatin solution and the disintegration of soft capsules, the proportion and formulation were determined. We established the preparation technology and prepared SV-SMEDDS soft capsules. The process of the soft capsule is stable and the quality is controllable, and it is suitable for industrialization.The soft capsules have been stored under stress testing conditions:light illumination (4500±500Lx), high humidity (RH75%, RH92.5%) and heat (60℃,40℃) for5and10days. The results showed that it was not stable under high temperature and should be stored under low temperature. In addition, accelerating and long term stability test to three consecutive batches of pilot manufacturing products were also investigated. The results of stability tests show that the quality of it is stable.