title: Solubility and stability enhancement of atorvastatin by cyclodextrin complexation.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, Maharashtra, India.
authors.forename: Chinna Reddy
authors.initials: CR
authors.lastname: Palem
authors.forename: Shweta
authors.initials: S
authors.lastname: Patel
authors.forename: Varsha B
authors.initials: VB
authors.lastname: Pokharkar
mesh_terms: D000069059:Atorvastatin; D002152:Calorimetry, Differential Scanning; D004355:Drug Stability; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry*; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D047392:beta-Cyclodextrins; D000069059:Atorvastatin; C031215:betadex