Study On Non - Clinical Pharmacokinetics And In Vitro Dissolution

Nicergoline,1 Oa-methoxy-1,6-dimethylergoline-8-methanol-5-bromo-3-pyridine carboxylate(ester), shows a-receptor blocking and vasodilating activity.The drug cause a decrease in cerebreal vascular resistance which is associated with an increase in oxygen consumption and an improvement of blood circulation and brain metabolism. Nicergoline has proved to have cerebral-anti-ischemic action, also exhibiting platelet antiaggregating and disaggregating action. It is effective clinically in chronic cerebral insufficiency and senile dementia due to insufficiency of blood in peripheral vessels.The concentration of nicergoline in plasma was determined by RP-HPLC method with UV-detecter after single oral doses of nicergoline tables and nicergoline caps to 8 beagle dogs. The study was designed in a crossover, random, two-treated, two-period test.Bioequivalence of the two formulation were evaluated by ANONA and the two one-side test. The in vitro release characteristic of two formulation were studied by determining their dissolution and evaluated with similarity factor method. The absorbed fractions were Loo-Riegelman’s formula, and a linear correlation was calculated by using percent dissolution data and percent absorbed data from two formulations at the corresponding times.The results of the pharmacokinetic parameters obtained after single oral administration of the two pantoprazole enteric coated tables were as following:Cmax were (442.1±47.5) and (429.6±46.9) ng/mL, Tmax were (1.75±0.70)and (2.06±0.62)h, t1/2 were (2.70±0.85) and (2.77±0.80)h, AUC0→24 were (2131.8±510.3) and (2203.8±308.2) ng-h/mL, AUC0→∞were (2295.2±497.0) and (2390.8±332.1) ng-h/mL for test and reference tablets, respectively. The relative bioavailability of the test tablet was 96.3±14.1%. The 90% confidence interval of AUC0→24 about the test table was 91.6%-106.9% by reference tablet; the 90% confidence interval of AUC0→∞about the test table was 94.3%-111.7% by reference tablet; the 90% confidence interval of Cmax about the test table was96.8%-106.8% by reference tablet.The resule show that the pharmacokinetic parameters obtained after single oral administration of the two nicergolines showed that there were no significant difference between two formulations in AUC0→24’ AUC0→∞and Cmax. The dissolution rates of two formulations were sufficient. There have no similarity between two dissolution curves, and in vivo and in vitro is not relevant.