Studies Of Famotidine Ph-independent Sustained Release Tablets

Famotidine is a structurally safe and efficient antipeptie ulcer drug with H₂- receptor antagonists properties. In this paper, famotidine is used as model drug to prepare pH-independent matrix tablets and pH-independent sustained release resin tablets. Furthermore, the release behaviors of famotidine in vitro and in vivo and the mechanism of two types of tablets were elementarily studied. The studies were composed as follows:1) In the studies, the famotidine pH-independent matrix tablets were prepared by direct powder compression method, HPMC was used as sustained release matrix material, incorporating with citric acid and Eudragit S100 as pH-modifier which can modifiy the "bust release". Single factor test results showed that the type and content of HPMC , the amount of citric acid and the amount of Eudragit S100 were important factors influencing drug release rate . The preparation method and rotate speed had effect on drug release rate, whereas the amount of additive, particle size of HPMC, diameter of tablet, compression force and pH value of medium had all no effect on drug release rate. The results of mechanism of drug release showed famotidine released by the synergic effect of diffusion and erosion from HPMC matrix.2) The drug-resin complexes were prepared by batch method and column method. The key factors were investigated, and combination mechanism of famotidine-resin complex was investigated by DSC, which ascertained that the combination force between famotidine and resin was ionic bond interaction instead of physical adsorption interaction. The studies of the drug release of drug-resin complex in vitro showed that the rate and amounts of famotidine release were increased with rising ion concentration. While temperature,the type of exchange ion and pH values of the release media had no obvious effect on the release behavior of drug-resin complex. The mechanism of release in vitro showed that the diffusion of famotidine from the resin particles was controlled by particle diffusion process according to Viswanathan's equation.3) The famotidine pH-independent sustained release resin tablets were prepared by using famotidine-resin complex, and single factor test results showed that the type and content of HPMC and the amount of citric acid were important factors influencing drug release rate. The type of additive, diameter of tablet and rotate speed had some effect on drug release rate, whereas particle size of HPMC, compression force and pH value of medium had all no effect on drug release rate.4) Using the conventional tablets as the references, the pharmacokinetic study of the self-made two kinds of 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 sustained release tablets were delayed, C_max were decreased. Good correlation existed between drug absorption percentage in vivo and drug release rate in vitro .