Preparation of Isosorbide Mononitrate Controlled Release Tablets and Evaluation of Their Bioavailability in Beagle Dogs

Objective To prepare isosorbide mononitrate controlled release tablets and study their pharmacokinetics and relative bioavailability in Beagle dogs.Methods Isosorbide mononitrate controlled release tablets were prepared by monolithic osmotic pump technique.These tablets and isosorbide mononitrate sustained release tablets(reference formulation) were given orally to Beagle dogs by a two-crossover design.Drug concentrations in plasma were determined by gas chromatography-electron capture detector and the pharmacokinetic parameters of isosorbide mononitrate were analyzed by DAS 2.0.Results The main pharmacokinetic parameters of the self-made controlled release tablets and reference formulation were as follows:t1/2 was(5.083±1.524)and(4.866±1.361)h,Cmax was(0.617±0.213)and(0.753±0.228)μg/ml,Tmax was(2.250±0.880) and(2.722±0.935) h;AUC(0-t) was(5.086±0.832)and(4.997±0.916)μg·h/ml,AUC(0-∞) was(5.254±0.754)and(5.258±1.032)μg·h/ml.The relative bioavailability was(101.0±17.7)%.Conclusion Compared with the sustained release tablets,isosorbide mononitrate controlled release tablets have a similar pharmacokinetic profile and the two formulations are bioequivalent.