Microwave induced solubility enhancement of poorly water soluble atorvastatin calcium

Abstract

Objectives The objective of the present investigation was to enhance the solubility and dissolution rate of atorvastatin calcium (ATR) by a solid dispersion technique using poly(ethylene glycol) 6000 (PEG 6000). Methods Microwave energy was used to prepare an enhanced release dosage form of the poorly water soluble drug ATR with PEG 6000 as a hydrophilic carrier. After the microwave treatment, the drug and hydrophilic polymer get fused together to form a solid dispersion. An in-vivo study was performed to determine the lipid-lowering efficacy (cholesterol, high density lipoprotein and triglyceride) of the solid dispersions using a Triton-induced hypercholesterolemia model in rats. Key findings An increase in the solubility of ATR was observed with increasing concentration of PEG 6000. The optimized ratio for preparation of solid dispersions of ATR with PEG 6000 was 1: 12 w/w by conventional fusion and the microwave induced fusion method. Differential scanning calorimetry and powder X-ray diffraction studies of the solid dispersions confirmed the conversion of some crystalline ATR into the amorphous form. Scanning electron microscopy images also showed conversion of some crystalline ATR into the amorphous form. The in-vitro study showed that solid dispersions increased the solubility and dissolution rate of ATR, and thus may improve its bioavailability compared with plain ATR. The solid dispersion formulation prepared by the microwave induced fusion method significantly (P < 0.05) reduced serum lipid levels in phases I and II (18 h and 24 h) of the Triton test compared with plain ATR. Conclusions The microwave induced fusion method could be considered as a simple, efficient method to prepare solid dispersions of ATR with significant enhancement of the in-vitro dissolution rate as well as in-vivo activity. © 2010 Royal Pharmaceutical Society of Great Britain.