PREPARATION AND IN-VIVO EVALUATION OF SIMVASTATIN CRYSTALLO-CO-AGGLOMERATES

The purpose of this research was to obtain directly compressible agglomerates of simvastatin using a crystallo-co-agglomeration technique and determine its in-vivo performance in rats. Simvastatin Dicalcium phosphate co agglomerates were prepared from Dichloromethane: Isopropyl Myristate: Distilled water system containing polyvinyl pyrrolidone (PVP). Dichloromethane acted as a good solvent for simvastatin, the water acted as a bad solvent, and isopropyl myristate acted as a bridging liquid for agglomeration. 2³ factorial design was used for optimization, wherein the factors were stirring speed, polymer concentration, and amount of bridging liquid. The responses evaluated were dissolution, b value, and Carr’s index. The agglomerates were characterized by powder x-ray diffraction (PXRD), which showed that there is a decrease in crystallinity or partial amorphization of the drug in its agglomerated form. Micromeritic and compression properties of the agglomerates were affected by an incorporated polymer. Dissolution of agglomerates (91.73%) increased as compared to a pure drug (25.96%). The agglomeration increased the flow property of Simvastatin which was indicated by Carr’s index of a drug (40.81) and an optimized batch of agglomerates (11.72). In-vivo pharmacokinetic studies on rats demonstrated increases in C_max and AUC of Simvastatin Dicalcium phosphate crystallo–co–agglomerates as compared to that of marketed formulation.