Studies On Compound Nimodipine And Aspirin Enteric Tablets

Recently research proved that the combination of nimodipine and aspirin could not only play roles of their original pharmacological effects but also provided synergistic activities. The two drugs yielded synergistic activities through inhibitory effects on platelet aggregation and obviously protective effects of brain tissue. To produce the synergistic activities of aspirin and nimodipine and reduce incident of side effects of aspirin, the compound nimodipine enteric tablets was studied. Nimodipine is a poorly water soluble substance, to increase the bioavailability of nimodipine, the nimodipne solid dispersion was studied as well.To determine the dissolution and the release percent of nimodipine, the UV spectrophotometry methord was developed. To determine the content of nimodipine and to study the physicochemical properties of nimodipine, a high performance liquid chromatography (HPLC) method was established. A HPLC method was developed for the determination of the physicochemical properties, content and release percent of aspirin. The methods mentioned above are proved to be of high susceptibility, and good specificity, which all fit the requirement of analysis. The solubility of nimodipine in water, O.1mol-L-1 HCL and pH6.8 phosphate buffers, as well as the apparent partition coefficient of nimodipen and aspirin in octanol-water system, were determined. The results showed that nimodipine was poorly soluble and lipophilic. The apparent partition coefficient of asprin was 4.82. The interaction of nimodipen and aspirin was studied, the results showed that the eutectic mixture of aspirin and nimodipine was formated when the mass percentage of aspirin was 15%, environmental temperature was 107℃, and hydrogen bonding or van der Waals force may be exist, but no new material generated.Based on single factor tests, the formulation of nimodipine solid dispersion was optimized through orthogonal design with accumulative dissolution in 45 minutes as index. The optimal formulation was nimodipine 1.0g, HPMCE5 4.0g, silica gel 0.5g and ethanol 24mL. Four methods, including DSC, XRD, SEM and IR were applied in the study of physicochemical characterization, the results showed that nimodipine was in amorphous state in the solid dispersion, it distributed in the carrier surface and pores, and it combined with material by hydrogen bonding. Stability study showed that the solid dispersion was stable under the condition of 75% RH in a month.Based on the investigation of the effects of excipients on powder technology properties of nimodipine solid dispersion (NMPSD) powders, the formulation of the core of the compound enteric-coated tablets was optimized by using the central composite design-response surface optimization methodology. The independent variables included the mounts of the talc and the CCNa. The dissolution at 30 minutes and the angle of repose were taken as dependent variables. The optimal formulation contained NMPSD41.95%, aspirin 2.10%, MCC41.95%, talc 3.00% and CCNal 1.00%.Two HPLC methods were developed for the determination of NMP and SA in dog biological samples respectly. The pharmacokinetics interaction of nimodipine and aspirin in dogs was studied comparing with the reference. The relative bioavailability of nimodipine and aspirin were129.96%and 79.13%. The result suggested that the nimodipine and the aspirin had pharmacokinetics interaction.