Studies On Bioequivalence And In Vitro/in Vivo Correlations Of Compound Niacin Sustained-release Tablets

Aim This study was to compare the bioavailability of niotinic acid sustained release tablets and niotinic acid common tablets and to investigate the correlation between in vitro release and in vivo absorption of two tablets.Methods The concentration of niotinic acid in plasma was determined by RP-HPLC method with UV-detection after single and multiple oral doses of tablets to 6 BeaGLE dog. 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 niotinic acid sustained release tablets were as following: The Tmax were (2.58±0.92)h and (1.00±0.17)h, Cmax were (107.8±10.12)μg·ml-1and (205.91±28.64)μg·ml-1, AUC(0-108h) were (469.3±75.45)μg·h·ml-1 and (507.31±47.56)μg·h·ml-1,MRT were (1.88±0.84)h and (1.06±0.26)h for test and reference tablets, respectively. The relative bioavailability of the test tablet was 91.16%. The similar factor was 24.03.After calculated by 3P97 software, the pharmacokinetic process of Niotinic acid sustained release tablets accord with one-compartment model, the correlation coeffcients are 0.9922 for test tablets.Conclusion The pharmacokinetic parameters obtained after single oral administration of the compound niotinic acid sustained release tablets and nicotinic acid common tablet showed that there were no significant difference between two formulations in AUC0-10, and there there were signifigant difference in Cmax, Tmax and MRT. The sustained release tablet was bioequivalent to RT and compound niotinic acid sustained release tablets possessed good sustained release property. The dissolution rates between two formulations were different and the dissolution was similar. The results of correlation test showed the compoumd nicotinic acid sustained release tablets had a satisfactory correlation between dissolution in vitro and absorption in vivo.