Bioequivalence evaluation of two brands of gliclazide 80 mg tablets (Glyzide^® & Diamicron^®) — in healthy human volunteers

Abstract

A randomized, two-way, crossover, bioequivalence study in 24 fasting, healthy, male volunteers was conducted to compare two brands of gliclazide 80 mg tablets, Glyzide (Julphar, UAE) as test and Diamicron (Servier Industries, France) as reference product. The study was performed at the International Pharmaceutical Research Centre (IPRC), in joint venture with Speciality Hospital, Amman, Jordan. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. After dosing, serial blood samples were collected for a period of 48 h. Plasma harvested from blood was analyzed for gliclazide by validated HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant), C(max), T(max), T(1/2), and elimination rate constant were determined from plasma concentrations of both formulations. Statistical modules (ANOVA and 90% confidence intervals) were applied to AUC(0-t), AUC(0- proportional, variant), and C(max) for bioequivalence evaluation of the two brands which revealed no significant difference between them, and 90% CI fell within US FDA accepted bioequivalence range of 80-125%. Based on these statistical inferences, Glyzide was judged bioequivalent to Diamicron.

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

“…The predicted fraction of drug absorbed (F a ) was 99.94% which is in accordance with the literature-reported almost 100% bioavailability of gliclazide after oral administration (1,2). The predicted and in vivo observed pharmacokinetic parameters following oral administration of 80-mg GLK IR tablets are shown in Table II.…”

“…A set of virtual in vitro data representing different dissolution scenarios was used as the input function in GastroPlus TM software to estimate the expected GLK in vivo absorption profiles. The profiles obtained were compared with the mean plasma concentration profile of gliclazide observed after oral administration of 80-mg tablets (2).…”

“…GLK is available as oral tablets (30 and 80 mg strength) with the recommended dosage between 40 and 320 mg/day. Reports from the in vivo studies show that, after oral administration, gliclazide is almost completely absorbed (1,2). However, due to its low and pH-dependent aqueous solubility (3)(4)(5), GLK absorption rate appears to be slow and variable (3,(6)(7)(8), and therefore, its absorption profile is difficult to decipher.…”

“…The purpose of this study was: (1) to develop a drugspecific absorption model for gliclazide using gastrointestinal simulation technology (GIST), (2) to use the generated absorption model to provide the target in vivo dissolution profile for IVIVC, and (3) to identify biorelevant dissolution specifications for GLK IR tablets based on a set of virtual in vitro data. Level A IVIVC based on deconvolution and convolution approaches were applied to assess the relationship between the in vitro and in vivo data.…”

In Vitro Interaction Between Oral Hypoglycemic Drug And Herbal Sex Stimulants: Drug Interactions

“…Gliclazide is available as oral tablets (30 and 80 mg strength) with the recommended dosage between 40 and 320 mg/day. Reports from the in vivo studies show that, after oral administration, gliclazide is almost completely absorbed (Delrat et al, 2002;Najib et al, 2002). However, due to its low and pH-dependent aqueous solubility (Hong et al, 1998;Özkan et al, 2000;Shewale et al, 2008), Gliclazide absorption rate appears to be slow and variable (Hong et al, 1998;Kobayashi et al, 1981;Davis et al, 2000;Rana, 2010), and therefore, its absorption profile is difficult to decipher.…”