Effect of Food on the Pharmacokinetics of Gliclazide 60 mg Modified Release Tablet in Healthy Caucasian Volunteers

Abstract

Objective: To evaluate the food effect on glicazide disposition in clinical trials conducted on healthy Caucasian volunteers who were given a new modified release oral formulation of Gliclazide 60 mg developed by Sun Pharmaceutical Industries, India.Methods: The studies were designed as open-label, randomized, single-dose, crossover studies that consisted of two periods. During each study, venous blood samples were taken before and after drug administration up to 96 hours. Subsequently, individual plasma profiles were determined and non-compartmental method was employed for the assessment of food effect on the pharmacokinetic profile of gliclazide. The statistical significance of differences for the main pharmacokinetic parameters was evaluated by ANOVA test, for p < 0.05 statistical significance was decided. The relative profiles of absorption of gliclazide were obtained by mathematical deconvolution. All calculation were performed by Phoenix WinNonlin®.Results: High-fat, high-calorie meal decreased gliclazide exposure. The mean maximum plasma concentration decreased with 14%, while the mean total area under the plasma concentration-time profile registered a 17% decrease. The elimination half-lives under fasted and fed conditions were comparable and the time to maximum plasma concentration was shortened under fed condition. Safety evaluation showed that overall gliclazide was well tolerated under both fasted and fed condition.Conclusions: The statistical analysis revealed the lack of food effect on the new modified release tablets of Gliclazide 60 mg. However, before stating a definite conclusion regarding the food effect on gliclazide pharmacokinetic profile, additional studies on patients with type 2 diabetes mellitus should be conducted.

In vitro – in vivo correlation for Gliclazide 60 mg modified release tablets

“…Thus, the relative fraction absorbed of gliclazide from the site of administration over time was obtained and is depicted in Figure 2. The data of the bioequivalence studies were previously reported [11,14,15]. In vitro studies By using the methodology and sample preparation described in the experimental section, the percent of dissolved gliclazide from the 60 mg modified release generic tablets were obtained, in three distinct dissolution media.…”

“…In vitro -in vivo correlation The in vitro-in vivo correlations (IVIVCs) were evaluated for level A correlation. Hence, the absorption profiles of Gliclazide 60 mg modified release tablets manufactured by Ranbaxy Laboratories Limited, now Sun Pharmaceutical Industries Limited, India, were obtained from the individual plasma drug concentration versus time profiles from the bioequivalence trials [11,14,15]. The absorption profiles were determined for both clinical trials performed under fasting or fed conditions.…”

“…Thus, IVIVC are probable in practice for API belonging to BCS class II (low solubility, high permeability) in drug dosage forms with slow release [18]. The newly developed generic tablet of gliclazide 60 mg was designed as a modified release (MR) formulation for which the tablet's hydration leads to formation of a gel layer through which the API is slowly released in time [11,14,15]. Hence, the drug dosage type controls the absorption of gliclazide and its low solubility is not a rate-limiting step for absorption.…”

“…Hence, the drug dosage type controls the absorption of gliclazide and its low solubility is not a rate-limiting step for absorption. Gliclazide MR was shown to have predictable and reproducible release of the API and effective plasma concentrations over a 24 hours' period taken as a single daily dose (30 -120 mg), thus assuring a hypoglycemic effect for a longer time-period [14,15,19,20].…”

“…After oral administration, it was reported that gliclazide displays a non-solubility-limited absorption. The absorption rate and the onset of action is delayed after oral administration [6,11,12,13]. Gliclazide has a wide therapeutic index and displays linear profile for doses up to 120 mg [19,20].…”