title: In vitro-in vivo correlation for gliclazide immediate-release tablets based on mechanistic absorption simulation.
abstract: The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented in GastroPlus(TM) software package. A range of experimentally determined, in silico predicted or literature data were used as input parameters. Experimentally determined pH-solubility profile was used for all simulations. The human jejunum effective permeability (P (eff)) value was estimated on the basis of in vitro measured Caco-2 permeability (literature data). The required PK inputs were taken from the literature. The results of the simulations were compared with actual clinical data and revealed that the GIST-model gave accurate prediction of gliclazide oral absorption. The generated absorption model provided the target in vivo dissolution profile for in vitro-in vivo correlation and identification of biorelevant dissolution specification for GLK immediate-release (IR) tablets. A set of virtual in vitro data was used for correlation purposes. The obtained results suggest that dissolution specification of more than 85% GLK dissolved in 60 min may be considered as "biorelevant" dissolution acceptance criteria for GLK IR tablets.
authors.affiliation: Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221, Belgrade, Serbia. gsandra@pharmacy.bg.ac.rs
authors.forename: Sandra
authors.initials: S
authors.lastname: Grbic
authors.forename: Jelena
authors.initials: J
authors.lastname: Parojcic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ibric
authors.forename: Zorica
authors.initials: Z
authors.lastname: Djuric
mesh_terms: D003198:Computer Simulation; D004304:Dosage Forms; D005907:Gliclazide / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption; D008954:Models, Biological; D010539:Permeability; D012984:Software; D012995:Solubility; D013607:Tablets
chemical_list: D004304:Dosage Forms; D007004:Hypoglycemic Agents; D013607:Tablets; D005907:Gliclazide