title: Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin.
abstract: The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The (1)H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC-MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0-t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture.
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors.forename: Meina
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road, Shenyang 110016, China. Electronic address: hezhonggui@vip.163.com.
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002219:Carbamates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D005612:Freeze Drying; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D053719:Tandem Mass Spectrometry / Q000379:methods; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C072379:repaglinide
keywords: Hydroxypropyl-; Inclusion complex; NMR spectroscopy; Pharmacokinetics; Phase solubility studies; Repaglinide; β-cyclodextrin