title: Matrix tablets for sustained release of repaglinide: Preparation, pharmacokinetics and hypoglycemic activity in beagle dogs.
abstract: Repaglinide (RG) is an efficient antihyperglycemic drug; however, due to its short half-life, patients are required to take the marketed products several times a day, which compromises the therapeutic effects. The present study was conducted to develop a hydrophilic sustained release matrix tablet for RG with the aims of prolonging its action time, reducing the required administration times and side effects and improving patient adherence. The matrix tablets were fabricated by a direct compression method, the optimized formulation for which was obtained by screening the factors that affected the drug release. Moreover, studies of the pharmacokinetics and hypoglycemic activity as measured by glucose assay kits were performed in dogs. Sustained drug releases profiles over 10h and a reduced influence of medium pHs on release were achieved with the optimized formulation; moreover, the in vivo performance of extended release formulation was also examined, and better absorption, a one-fold decrease in Cmax, a two-fold increase of Tmax and a prolonged hypoglycemic effect compared to the marketed product were observed. In conclusion, sustained RG release and prolonged action were observed with present matrix tablets, which therefore provide a promising formulation for T2D patients who require long-term treatment.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxing, Nanjing 210009, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxing, Nanjing 210009, PR China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Wu
authors.affiliation: The Third People's Hospital of Chengdu, Chengdu 610031, PR China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxing, Nanjing 210009, PR China. Electronic address: lifangyin@hotmail.com.
authors.forename: Lifang
authors.initials: L
authors.lastname: Yin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002219:Carbamates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004285:Dogs; D065546:Drug Liberation; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010880:Piperidines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013607:Tablets
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D010880:Piperidines; D013607:Tablets; C072379:repaglinide
keywords: Hypoglycemic effect; In vitro/in vivo correlation; Pharmacokinetics; Repaglinide; Sustained release tablets