title: Preparation, physicochemical characteristics and bioavailability studies of an atorvastatin hydroxypropyl-beta-cyclodextrin complex.
abstract: The aim of this study was to improve the solubility, stability and bioavailability of amorphous atorvastatin calcium (AT) by complexing it with hydroxypropyl-beta-cyclodextrin. The formation of the inclusion complexation was identified by molecular modeling, phase solubility diagrams, differential scanning calorimetry and X-ray powder diffractometry. Orally Disintegrating Tablets (ODT) were then manufactured by direct compression. Apart from improved stability compared to pure AT, disintegration time of 27s, hardness of 5 kg and favorable mouth feel were achieved. In vitro dissolution tests of the ODT of AT inclusion complex exhibited higher dissolution rates than those with pure drug and the commercial tablet Lipitor. In vivo bioavailability studies in rats also showed shorter T(max), higher C(max) and increased AUC of 4.42 and 1.86 fold compared to the plain drug ODT and Lipitor. These results strongly suggest to use HP-beta-CD to improve the physicochemical characteristics and bioavailability of AT.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
authors.forename: Hu-Xia
authors.initials: HX
authors.lastname: Lv
authors.forename: Zhen-Hai
authors.initials: ZH
authors.lastname: Zhang
authors.lastname: Hui-Jiang
authors.forename: Ayman Y
authors.initials: AY
authors.lastname: Waddad
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhou
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D000069059:Atorvastatin; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004563:Electrochemistry; D005079:Excipients; D006244:Hardness; D006538:Heptanoic Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011758:Pyrroles / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013607:Tablets; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000069059:Atorvastatin