Studies On Esomeprazole Magnesium Enteric Coated Pellets Tablet

Esomeprazole magnesium(bis-s-5- methoxy-2- [(4-methoxy- 3,5- dimethyl-2-pyridinyl) methyl] methylene sulfonyl-1H- benzimidazole magnesium trihydrate) was the L-isomer of omeprazole, which could be concentrated and converted to the active form in the highly acidic environment of secrete acid microtubules of parietal cells and be more effective control of gastric acid levels compared with omeprazole. Compared with dextrorotatory isomer of omeprazole, esomeprazole magnesium had a more stable optical qualities, negligible side effects and higher oral bioavailability. Because sulfonyl of esomeprazole magnesium was extremely sensitive to acidic solution, the drug was easily degraded by the catalysis of acidic compounds. Taking into account of the physical and chemical properties of the drug, patient’s compliance, divided doses and other factors, multiparticulate tablet was selected as the preferred dosage form and a systematic study of the preparation processes were carried out.Together with a suitable proportion of tabletting excipients, pellets were prepared to multiparticulate tablet, which possessed certain drug release characteristics. Compared with capsules, multiparticulate tablet have a good compliance, risk-free of burst release and lower production costs. Meanwhile, the bioavailability and stability of the drug had also been improved. Compared with the release character of the multiparticulate tablet, the intersected tablet still kept the original release features, which providing more selective for clinical use, especially for narrow therapeutic index drugs that need to be adjusted dose.The research background of drugs, physical and chemical parameters and pharmacokinetic parameters were introduced in the first part of this article. Secondly, it introduces the principles of equipment and technology needed for the research. Finally, the pellet and multiparticulate tablet dosage form was briefly introducted.In accordance with the physicochemical properties of esomeprazole magnesium, HPLC method was established to measure the content and in vitro release of esomeprazole magnesium pellet and tablet. The above method can accurately and quickly detect the in vitro drug release behavior.The third part of this article is the preparation of esomeprazole magnesium enteric-coated pellets. To protect the drug from degradation by stomach acid, acrylics was selected as enteric coating material to prepare esomeprazole magnesium enteric-coated pellets by bottom spray fluid bed. First, the drug-containing coating solution is spayed to the blank sucrose for the preparation of drug-loaded pellets using bottom-spray fluidized bed method. In the durg-loaded preparion stage, the drug substance to binder ratio and the concentration of adhesives and drug suspension solutions were optimized to assess its effect on drug layering efficiency. Secondly, to prevent drug from contacting with the acidic enteric coating material, HPMC was chosen as isolation layer coating material. In the isolation layer preparation stage, the weight gain and concentration of the HPMC solutions were respectively optimized to assess the formula and preparation technology. Finally, different proportions of Eudragit L30D-55 and Eudragit NE30 D mixed solutions were prepared to prepare enteric coated pellets. In the enteric coating stage the Eudragit L30D-55 to Eudragit NE30 D ratio, the content of the plasticizer, the coating weight gain and the aging time were respectively optimized to assess the enteric coated formulation and preparation technology. The particle size and particle size distribution of enteric-coated pellets, bulk density, tap density, angle of repose and friability were selected as evaluation indicators to assess the micromateritics characteristics.Using Box-Behnken design analysis, the hardness, disintegration time, acid tolerance and release were chosen as indexes to optimize the tablet formulations and preparation technology, which established a foundation for the further development of multiparticulate tablet.A preliminary stability research for pellets was carried out. According to the appearances, acid tolerance, release, content and content uniformity, the influencing factors test and accelerated test of three months were carried out to investigate the stability of esomeprazole magnesium enteric-coated pellets. The results showed that esomeprazole magnesium enteric-coated pellets was unstable at a high temperature, high humidity and light conditions, which suggested that the pellets should be stored at a dry place and lucifuge. The results of accelerated testing indicated that the multiparticulate pellets was stable after three months.