Study And Preparation On Sodium Rabeprazole–resinate Microcapsules

Objective:Rabeprazole sodium is a new generation of highly efficient, quick and safe proton pump inhibitors, it is the first selection medicaments with treatment of gastroesophageal reflux disease and gastric acid related diseases. But it is not very stable and susceptible to be degradation in acid, oxidation, light and thermal conditions.In this paper, Rabeprazole sodium was used as model drug and resin as the carrier,a new Rabeprazole-resinate complex was designed through ion exchange adsorption technology. Then, The drug-resinate microcapsules were prepared by emulsion solvent evaporation method, which can improve its stability and moistureproof performance.Methods:High Performance Liquid Chromatography(HPLC) was established for detecting the amounts of drug-loading, drug vitro release tests and content determination assaying tests. The drug-resin complexes(RBZ) were prepared by batch method of ion exchang. Exchange resin dosage and the drug utilization regard as comprehensive evaluation index, The key factors influencing(such as initial concentration, drugs resin ratio, temperature, solution ionic strength) on exchange resin dosage and the drug utilization were investigated. The best preparation technology was obtained by singlefactor investigation. Then the preparation technology was further optimized by orthogonal test. The combination mechanism of drug-resinate complexes was investigated by microgram, infrared spectrum, X-ray diffraction and differential thermal scanning method. The moistureproof property curve with rabeprazole sodium,blank resin and drug resin compound was drawn in 32.5%, 57.5%, 75.8%, 92.5%different humidity conditions. The optimum release conditions was determined through inspecting the influence of release conditions and the release medium for drug release. The microcapsule were prepared with the emulsion solvent evaporation method and ethylcellulose(EC) was used as coating material. Respectively investigates the coating process factors(such as stirring speed, curing temperature and curing time) and coating prescription factors(such as the ratio between drug-resinate and EC, capsule material concentration and the percentage of plasticizer), the optimum coating formulation and reaction condition were acquired by evaluating the drug loadings and the drug release behavior of the microcapsule.Result:1.High-performance liquid chromatography(HPLC) was applied to the determination of drug concentration of, which was proved strong specificity, short analysis time(10 minutes) and high detection sensitivity.2.Rabeprazole-resinate complexes was prepared by orthogonal test. The best preparation process was as follows,,the liquid was 0.001 mol/L Na OH solution, the initial concentration was 1.0 mg/ml, drug resin ratio was 1:1.8 under 30 ℃.3. The combination mechanism of RBZ-resin was investigated by IR,DSC and X-ray diffraction analysis, which ascertained that the combination force between RBZ and resin was ionic bond interaction instead of physical adsorption interaction.4.The study of moistureproof performance showed that Rabeprazole-resinate complexes was obviously higher than that of rabeprazole sodium and blank resin.5.The factors affecting drug release from Rabeprazole-resinate complexes were investigated in different release conditions and release medium environment.Consequently the drug release experiment was carried out using 900ml0.15mol?L-1Na Cl solution as release medium in vitro with 50 rpm rotate speed at37℃.6.The best preparation technology of microcapsules was determined by investigating the coating process and prescription factors. Consequently drug resin and capsule material ratio was 4:1, capsule material concentration is 6 %(w/w), The percentage plasticizer of capsule material quality is 7 %. Mixing 4 hours under 400 rpm at 35 ℃. The drug release from the microcapsules followed first order kinetics characteristics. The repeatability of three batches was good.Conclusion:In this article rabeprazole sodium was used as model drug to make a drug-resinate microcapsule, which was taken 150 mg every time. It improved the stability of drugs and moisture-proof performance, it also presented advantages such as steady release rate、easiness to divide. The preparation technology of microcapsule is simple, low cost, easy to further preparation. The preparation can expand potential clinical application of rabeprazole sodium, and has high scientific value and good application prospect.