Solubility and stability enhancement of atorvastatin by cyclodextrin complexation.

The objective of the study was to increase the solubility, stability, and dissolution rate of atorvastatin calcium (ATN Ca), a poorly water-soluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) reductase inhibitor through inclusion complexation with beta-cyclodextrin (beta-CD). The phase solubility profile indicated that the solubility of ATN Ca was significantly increased in the presence of beta-CD and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by physical mixing, kneading, co-evaporation, and freeze-drying methods were characterized using differential scanning calorimetry, fourier transform infrared spectroscopy, and powder X-ray diffractometry. In vitro studies showed that the solubility and dissolution rate of ATN Ca were significantly improved by complexation with beta-CD with respect to the drug alone. In contrast, freeze-dried product showed higher solubility and dissolution rates than the other complexes. ATN Ca unit dosage form was developed and evaluated for physico-chemical properties, stability, and dissolution rate. The stability of tablets was studied and no significant changes were detected in the dissolution profile of tablets after 1 month.