title: Sustained-release of Cyclosporin A pellets: preparation, in vitro release, pharmacokinetic studies and in vitro-in vivo correlation in beagle dogs.
abstract: The aim of this study was to develop Cyclosporin A (CsA) sustained-release pellets which could maintain CsA blood concentration within the therapeutic window throughout dosing interval and to investigate the in vitro-in vivo correlation (IVIVC) in beagle dogs. The CsA sustained-release pellets (CsA pellets) were prepared by a double coating method and characterized in vitro as well as in vivo. Consequently, the CsA pellets obtained were spherical in shape, with a desirable drug loading (7.18 ± 0.17 g/100 g), good stability and showed a sustained-release effect. The Cmax, Tmax and AUC0-24 of CsA pellets from the in vivo pharmacokinetics evaluation was 268.22 ± 15.99 ng/ml, 6 ± 0 h and 3205.00 ± 149.55 ng·h/ml, respectively. Compared with Neoral®, CsA pellets significantly prolonged the duration of action, reduced the peak blood concentration and could maintain a relatively high concentration level till 24 h. The relative bioavailability of CsA pellets was 125.68 ± 5.37% that of Neoral®. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the pellets. In conclusion, CsA pellets which could ensure a constant systemic blood concentration within the therapeutic window for 24 h were prepared successfully. Meanwhile, this formulation possessed a good IVIVC.
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Dongmei
authors.initials: D
authors.lastname: Jiang
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Guanghui
authors.initials: G
authors.lastname: Zhou
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Wenwen
authors.initials: W
authors.lastname: Deng
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;
authors.forename: Ximing
authors.initials: X
authors.lastname: Xu
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University , Zhenjiang , China ;|b School of Pharmacy, China Pharmaceutical University , Nanjing , China.
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Cyclosporin A; double coating; in vitro release; in vitro–in vivo correlation; pharmacokinetic studies; sustained-release pellets