Preparation and Pharmacokinetics of Nifedipine Osmotic Pump Tablets in rabbits

Objective: To investigate the formulations and pharmacokinetics of nifedipine double-layer osmotic pump tablets.Methods: In present study,nifedipine was as the model drug to prepare the bi-layer osmotic pump tablets.The effects of many factors including formulation of drug layer,push layer and membrane,release media on the in-vitro release behavior of nifedipine tablets were investigated.The plasma nifedipine concentration of osmotic pump tablets and self-prepared ordinary tablets after single oral administration in rabbits were determined by HPLC.The pharmacokinetic parameters were calculated with the DAS 2.0 software.Results: The comprehensive formulation research showed that the release profile was influenced by PEO(POLYOX WSR N-12K) level of both layers and the diethyl phthalate(DEP) amount.The in-vivo pharmacokinetics research showed that the drug concentration-time curves fitted to a two-compartment model.The pharmacokinetic parameters for the single oral administration of the osmotic pump tablets and ordinary tablets were tmax(12.05±0.28) h and(5.98±0.47) h,Cmax(0.299±0.035) mg·L-1 and(0.452±0.038) mg·L-1,AUC0-∞(4.010±0.353) mg·h·L-1 and(3.355±0.441) mg·h·L-1,respectively.The relative bioavailability of osmotic pump tablets was 119.5%±7.2%.Conclusion: The results indicated that the optimal formulation had the excellent zero-order release character in vitro from 0-24 hours,and had the slow releasing characteristics after single dosage administration in rabbits.