Studies On Famotidine And Trimebutine Maleate Compound Two-Layer Tablets

Recently, clinical research proved that in the treatment of peptic ulcer, the combination of antacid and gastrointestinal motility regulator could provide better therapeutical effect and at the same time improve the disorder of gastrointestinal motility. In this study, famotidine and trimebutine maleate were selected to develop a compound product Famotidine is widely used as anti-ulcer agent and trimebutine maleate may exert unique opposing actions, i.e. an accelerating action in a hypokinetic state and an inhibitory action in a hyperkinetic state. According to the properties of the two drugs, famotidine was prepared as fast release layer and trimebutine maleate as sustained release layer.In order to provide the basis for the combination of this two drugs, the influence of trimebutine maleate on the therapeutical effect of famotidine in rats and mice was investigated from pharmacodynamic point of view. In this article, several gastric ulcer models were chosed. The effects of combination of the two drugs on gastric emptying and intestinal propulsive function were studied as well.Based on what have been studied above, studies on compound preparation were carried out as following:At first, ultraviolet (UV) spectrophotometry method was developed for determination of physicochemical properties, drug release and content ; High-performance liquid chromatography (HPLC )method was applied to determine the content and drug release of compound two-layer tablet. Precision and recovery met the request of methodology.Secondly, influencing factors such as formulation, technology and dissolutions conditions on the release of TM sustained release layer were investigated, on the basis of which formulation was optimized by fraction method. To decide the best formulation of FMTD fast released layer, orthogonal experiment design was employed. Compared with single layer tablet, compound two-layer tablet has no significant difference on appearance, content and drug release. Ritger-Peppas equation was used to study the releasing mechanism of TM sustained layer. The results showed that the mechanism of TM sustained layer was non-Fickian diffusion, in which matrix erosion played an important role.The results of preliminary stability experiments indicated that compound two-layer tablet had no changes in appearance, content and drug release under other conditions except high temperature.