Study Of The Ranitidine Bismuth Citrate Gastric Retenting-floating Sustained-release Tablet

Ranitidine bismuth citrate (RBC) is a new chemical entity which has been approved in many countries as a therapy for peptic ulcer and recommended as one of the first line therapies for eradication of H.pylori (Hp) due to its characteristics of gastric acid inhibition, gastric mucosal protection, Hp suppressing, gastrin and pepsin inhibition and synergy with antibiotics. RBC is chiefly to absorb in the stomach and on the small intestine, or directly act in the stomach. The time of common preparation in the stomach is short. And the common preparation can't have the good efficacy. We prepared the ranitidine bismuth citrate gastric retenting-floating sustained-release tablet (RBC-GRFSRT) in order to lengthen RBC in the stomach, and increase it's action in the stomach. The major content and result is as follows:Methods of the in-vitro release and the content determination were developed. The method of affinity factor is applicated to appraise the releasing of drug in-vitro medicine the explaining action of preparation. The method of directly observation and the buoyancy measurement is used to detect the floating capability of RBC-GRFSRT. The buoyancy measurement is be made ourselves. Both methods had good linearity, sufficient recovery and good accuracy et al.The formulation and process of preparing RBC-GRFSRT were optimized by one factor analysis law. The release percentage and floating capability of RBC-GRFSRT fitted the regulation. The mechanisms of RBC-GRFSRT release from once-daily dosage form were investigated. After fitting data of cumulative release from RBC-GRFSRT to some sorts of kinetic models, we found that RBC release curve have a good correlation coefficient in Higuchi equation. So we can suppose both diffusion and erosion are involved during the period of release.With the best formulation selected ,we made some batches of RBC-GRFSRT and carried out the accelerated testing and long-term testing. Results showed that those batches didn't make conspicuous changes in 6 months.RBC-capsules were used as control to study the pharmacokinetics andbioavailability of gastric retenting-floating sustained-release tablets in dogs. A specific and sensitive high-performance liquid chromatographic method for the determination of RBC in dog's plasma was described. Results showed that concentration-time curve could be explained by two-compartment model. Tmax=3.5h, MRT=7.9h, AUC= 36054.44 ng*h/ml, Cmax = 5896.98ng/ml. The relative bioavailability was 261.19%. Study showed the self-made tablets can achieve sustained release and increase drug activity in the extend of absorption between self-made tablets and control capsules.