Studies On Bioequivalence And In Vitro/in Vivo Correlations Of Gliclazide Sustained-release Tablets In Healthy Volunteers

Aim This study was to compare the bioavailability of two gliclazide sustained release tablets and to investigate the correlation between in vitro release and in vivo absorption of two tablets.Methods The concentration of gliclazide in plasma was determined by RP-HPLC method with UV-detection after single and multiple oral doses of tablets to 18 healthy male volunteers. The study was designed in a crossover, random, two-treatment, two-period test, the bioequivalence of the two formulations was evaluated by ANONA and two one-side t test. All data were treated by the Practical Pharmacokinetic Program Version 97 (3p97) and pharmacokinetic parameters were calculated. The in vitro release characteristics of two formulations were studied by determining their dissolution and evaluated with similarity factor method. The absorbed fractions were calculated by Wagner-Nelson' s formula, and a linear correlation was evaluated by using percent dissoluted data and percent absorbed data from two formulations at the corresponding times.Results The pharmacokinetic parameters obtained after single oral administration of the two gliclazide sustained release tablets were as following: The Tpeak were (8. 4 ± 3. 0)h and (9. 1 ± 3. 2)h, Cmax were (2.41 ± 0.06) μg·ml^-1and (2.24 ±0.55)μg?ml^-1, AUC_0-48h were (48.3 ± 16.4) μg ?h?ml^-1 and (47.4±15.9) μg ? h ? ml^-1, MRT were (17.1±2.0)h and (17. 3 ± 1.9)h for test and reference tablets, respectively. The relative bioavailability of the test tablet was 102. 4%. The parameters after multiple-dose indicated their Tpeak were (7.6 ± 3. l)h and (7. 1 ± 3. 2)h, Cmax were (3.33 ± 0.95) μg?ml^-1 and (3.00 ±0.83) μg ? ml^-1,...