In Vitro–In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation

Abstract

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.

Development of a Dissolution Method for Gliclazide Modified-Release Tablets Using USP Apparatus 3 with <i>in Vitro–in Vivo</i> Correlation

“…2) confirmed the low solubility of the drug in acid media and its general pH-dependent solubility profile as expected from previous reports. 5,7) Under the most acidic condition (pH 1.2), the solubility was slightly higher than pH 4.5-5.8 before increasing with the rise in alkalinity to a neutral pH. The range of pH 3.0-4.2 was previously reported as the main solubility-limited range for GLZ, 7) from which the solubility gradually increases.…”

“…5,7) Under the most acidic condition (pH 1.2), the solubility was slightly higher than pH 4.5-5.8 before increasing with the rise in alkalinity to a neutral pH. The range of pH 3.0-4.2 was previously reported as the main solubility-limited range for GLZ, 7) from which the solubility gradually increases. In addition, the solubility of this drug is described as the limiting factor for absorption up to pH 6.9.…”

“…In addition, the solubility of this drug is described as the limiting factor for absorption up to pH 6.9. 7) The lower solubility in acid medium is generally considered a problem in the design of an immediate-release (IR) dosage form for GLZ because the entire dose should be rapidly released in the upper part of GIT. 33) However, the MR tablets of the GLZ were formulated with a hydrophilic matrix to obtain a more consistent and less pH-dependent release.…”

“…4,5) The pH-dependent solubility of GLZ was suggested to be a relevant factor for its slow absorption in the gastrointestinal tract (GIT). 6,7) To improve its availability, modified-release (MR) tablets of the drug were formulated with a hydrophilic matrix to obtain a more consistent and less pH-dependent release profile of the active pharmaceutical ingredient over a 24 h period. 8,9) The formulation can be administered before, during or after meals.…”

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies

“…The input parameter required for P eff simulation was experimentally determined based on permeability studies using the Caco-2 cell line. 21 In the physiology tab, the default values for transit time were selected for each compartment, with the fasted option checked. Pharmacokinetic parameters, such as clearance and distribution volume, were used in the pharmacokinetic tab for simulation by Gastroplus.…”