Famotidine, Penetration Of The Pump Preparations

Famotidine is a structurally safe and efficient antipeptie ulcer drug with H_2- receptor antagonists properties. In this paper, famotidine is used as the model drugs to prepare compound monolith osmotic tablet(EOP) and push-pull osmotic pump controlled release tablets(PPOP). Furthermore, the release behaviors of both drugs in vitro and in vivo and the mechanism of two types of controlled release tablets were elementarily studied.Until now, there was no report about compound famotidine controlled release preparations in the research area of pharmacy. In this paper, compound famotidine controlled release tablets were developed. The effects of many factors including formulation of drug layers, arts of tablets and the condition of drug release on both drug release behaviors of monolith osmotic tablet were investigated, In general, both highly and poorly water-soluble drugs were not good candidates for elementary osmotic delivery. So, it was a great challenge to the pharmacists how to provide EOP with satisfactory controlled release behaviors of famotidine. In this paper, citric acid was used to modulate the solubility of famotidine within the core. In the paper , based on the investigation of factors analysis,orthogonal experiment designs were used to optimize the formulation. The results indicated that the drug release profiles of the optimal formulation had excellent zero-order release character in vitro(r=0.9926) from 0-24 hours.Under the condition of constant coating parameters, single factor tests were carried out on the formulation of tablet core and coating material, procedure as well as the in vitro release condition ,which affect the release behavivor were analyzed by similar factor method. Results showed that the amount of PEO_N1 of the drug layer , the amount of PVP and WSR1 in the assist layer, the amount and the kinds of PEG, the weight of coating all influence the drug release behavior ,while the diameter of orifice, the release medium and the method of dissolution had no significant effects. Hardness of tablet core also had no obvious effect on the release behavior of controlled release famotidine tablets. The results indicated that the drug release profiles had good zero-order release character and recuracy in vitro. The method of detecting drug concentration in plasma was based on the reference and our own exploration. Using the conventional tablets as the references, the pharmacokinetic study of the self-made two kinds of controlled release tablets were performed in six healthy Beagle dogs. After three cross studies, the concentrations of both drugs in plasma of dogs administered with single dose were detected by HPLC methods. The results showed that, T_max and MRT of the self-made two kinds of controlled release tablets were delayed, C_max were plaied down. Good correlation existed between absorption percentage in vivo and release rate in vitro .