title: Release behavior of tanshinone IIA sustained-release pellets based on crack formation theory.
abstract: The objective of this study was to investigate the drug release mechanism and in vivo performance of Tanshinone IIA sustained-release pellets, coated with blends of polyvinyl acetate (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A formulation screening study showed that pellets coated with PVAc-PVA-PEG at a ratio of 70:30 (w/w) succeeded in achieving a 24 h sustained release, irrespective of the coating weight (from 2% to 10%). Both the microscopic observation and mathematical model gave further insight into the underlying release mechanism, indicating that diffusion through water-filled cracks was dominant for the control of drug release. In vivo test showed that the maximum plasma concentration of sustained-release pellets was decreased from 82.13 ± 17.05 to 40.50 ± 11.72 ng mL as that of quick-release pellets. The time of maximum concentration, half time, and mean residence time were all prolonged from 3.80 ± 0.40 to 8.02 ± 0.81 h, 4.28 ± 1.21 to 8.18 ± 2.06 h, and 8.60 ± 1.59 to 17.50 ± 2.78 h, compared with uncoated preparations. A good in vitro-in vivo correlation was characterized by a high coefficient of determination (r = 0.9772). In conclusion, pellets coated with PVAc-PVA-PEG could achieve a satisfactory sustained-release behavior based on crack formation theory.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
authors.forename: Jikun
authors.initials: J
authors.lastname: Yang
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Fan
mesh_terms: D045784:Abietanes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011817:Rabbits; D027561:Salvia miltiorrhiza / Q000737:chemistry
chemical_list: D045784:Abietanes; D002316:Cardiotonic Agents; D003692:Delayed-Action Preparations; D004365:Drugs, Chinese Herbal; D011145:Polyvinyls; C021751:tanshinone; C013215:polyvinyl acetate; D011092:Polyethylene Glycols