In vitro-in vivo correlation of gliclazide

• Main Author: 周筱樺
• Other Authors: 許明照
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/60720928088468691451

碩士 === 臺北醫學大學 === 藥學系 === 92 === The aim of this study was to develop an in vitro-in vivo correlation (IVIVC) of gliclazide as a surrogate for bioequivalence when formulation changes or process modifications. Hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (Avicel® PH 101) and lactose were used to formulate tablets with three different release rates. The direct compression method was employed to prepare 240mg tablets containing 80mg gliclazide. Firstly, the influence of the various adding amount of sodium lauryl sulfate (SLS) on pH-solubility of gliclazide was examined. In vitro dissolution data were collected for each formulation using the ChP Apparatus II in three media of pH 1.2, pH 4.5 + 1% SLS, and pH 6.8 buffers stirred at 50rpm and in a pH change medium stirred at 100rpm and 150rpm. In vivo plasma concentration data were obtained from 18 healthy volunteers after administration of three different release rate dosage forms in a three-way crossover study. The pharmacokinetic parameters (Tmax, Cmax, AUC0-24 and AUC0-inf) were calculated as in vivo parameters to construct in vitro-in vivo correlation of level C. Direct mathematical deconvolution approach was utilized to calculate the fraction of drug absorbed to construct level A IVIVC. Percent prediction error (%PE) was estimated for Cmax and area under the curve (AUC) to determine the validity of the correlation. Linear level C IVIVC models with high correlation coefficient (r2＞0.9) in pH 1.2, pH 6.8 buffers and a pH change medium(150rpm) were successfully developed and had acceptable %PE. The best choice for constructing level A IVIVC was to conduct dissolution measurement in a pH change medium stirred at 150rpm. These constructed IVIVC correlations was expectable to be useful as a surrogate for bioequivalence when formulation changes or process modifications.