Improved bioavailability of Azelnidipine gastro retentive tablets-optimization and in-vivo assessment

Azelnidipine, dihydropyridine based calcium channel blocker has been used for treating ischemic heart disease and cardiac remodeling after myocardial infarction but it is having a low bioavailability due to its poor solubility. The present study is to investigate the formulation and evaluation of floating tablets of Azelnidipine for controlled release and to increase bioavailability by increasing the gastrointestinal transit time and mucoadhesion of drug. The gastro retentive tablets were prepared by direct compression method using different concentrations of combination of Polyoxyethylene oxide WSR 303 as hydrophilic polymer and Potassium bicarbonate as gas generating agent. Main effects of the formulation variables were evaluated quantitatively using design approach showing that both independent variables have significant effects on floating lag time, % drug release at 1 h (D1 h) and time required to release 90% of the drug (t90). The statistically optimized formulation (F3) released 95.11 ± 1.43% drug for 12 h followed K-Peppas drug release kinetics indicating release of drug by diffusion and erosion mechanism. Evaluation of the optimized formulation in vivo in human volunteers showed that the GFT was buoyant in gastric fluid and that its gastric residence time was enhanced. Pharmacokinetics studies carried out revealed significant (P < 0.05) equivalent Cmax, longer Tmax and higher AUC values for the optimized formula compared to the marketed oral product. From the results obtained it can be concluded that Azelnidipine Gastro retentive tablets with enhanced bioavailability and better release pattern is suitable for more effective treatment compared to marketed conventional tablets.