BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF MICRONIZED GLICLAZIDE IN HUMAN PLASMA BY LC-MS/MS AND ITS PHARMACOKINETIC STUDIES

Abstract

Drugs having poor oral bioavailability, fail to reach the minimum effective concentration required to achieve pharmacological action. Improvement of the oral bioavailability of the drug is the most realistic approach, as it is the most preferred and convenient route of administration. Besides numerous techniques to improve oral bioavailability of the drugs, particle size reduction leads to increase in the effective surface area, resulting in enhancement of solubility and dissolution velocity of the drug. In the present study a sustained release tablet formulation containing 60mg micronized gliclazide was attempted to develop and a randomized, two period, two treatment crossover, single dose, pilot study of test preparation along with a marketed sample of Gliclazide 60mg was carried out on 6 healthy male, adult, human volunteers under fasting condition to establish the bioequivalence of the new formulation with a washout period of one week. The developed method was found to be simple, reproducible, sensitive, and specific for the determination of gliclazide from plasma and was also applied to study the pharmacokinetic parameters of gliclazide. The mean peak plasma levels of gliclazide with the reference preparation on the study day ranged between 2562.27–2823.61ng/mL, while the test preparation ranged between 3091.24–3467.66ng/mL. On the basis of comparison of the AUC0-t for gliclazide after single dose administration, the relative bioavailability of the test preparation was 109.96% of that of the reference preparation.