title: Preparation and in vitro-in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability.
abstract: The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP(1) and NCAP(1)) or insoluble polymer alone (referred to as CAP(2) and NCAP(2)). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro-in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP(2), NCAP(1) and NCAP(2) were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C(max), T(max) and AUC((0→24)) of CAP(1) were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/mlh), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/mlh) for IRT. The relative bioavailability of CAP(1) was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability.
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103 Shenyang 110016, China.
authors: Lishuang
authors: L
authors: Xu
authors: Yanfei
authors: Y
authors: Luo
authors: Jia
authors: J
authors: Feng
authors: Ming
authors: M
authors: Xu
authors: Xiaoguang
authors: X
authors: Tao
authors: Haibing
authors: H
authors: He
authors: Xing
authors: X
authors: Tang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry; D004176:Dipyridamole / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C477852:Eudragit L 30 D-55; C477853:Eudragit NE 30-D; D008689:Methacrylates; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D013608:Tablets, Enteric-Coated; D019343:Citric Acid; D004176:Dipyridamole