Studies On Preparation Of Enteric-coated Pellets Comprising Esomeprazole Sodium Or Esomeprazole Magnesium Trihydrate

Objective:To study the adaptability of esomeprazole sodium and esomeprazole magnesium trihydrate during the course of preparation of enteric-coated pellets tablet and find out the preparation methods to obtain the enteric-coated pellets tablet.To carry on comparative studies on release behavior and stability of these enteric-coated pellets and compress the more suitable enteric-coated pellets comprising esomeprazole salt into a multiparticulate tablet.Methods:First,examined the in vitro release by ultraviolet spectrophotometry,determined the content and related substance of esomeprazole sodium or esomeprazole magnesium trihydrate by high performance liquid chromatography(HPLC).The physicochemical properties and the stability of the two active ingredients were simultaneously studied.Taking releasing rate,acid resistance and stability as indicators,the formulation and preparation process were investigated by single-factor test.Systematic evaluations of enteric-coated pellets comprising esomeprazole sodium or esomeprazole magnesium trihydrate,which were prepared under the same procedures using the same excipients,were carried out.Finally,the more suitable enteric-coated pellets comprising esomeprazole salt were compressed into a multiparticulate tablet.Results:The results of method validation indicated that the HPLC method was fit for the determination of content and related substance and the ultraviolet spectrophotometry was fit for the examination of in vitro release.The solubility of esomeprazole sodium in purified water is higher than that of esomeprazole magnesium.But the stability of esomeprazole sodium is poorer than that of esomeprazole.After the investigation and optimization of the formulation and processes of preparation,enteric-coated pellets comprising esomeprazole sodium or esomeprazole magnesium were obtained with good acid resistance and quick in vitro release rate in simulated intestinal fluid.The results in the comparative studies showed that the release rate of enteric-coated pellets comprising esomeprazole sodium was slightly higher than that of enteric-coated pellets comprising esomeprazole magnesium.However,the stability of enteric-coated pellets comprising esomeprazole sodium was easier to have color changing and produce related substance in the preparation process and the accelerated test.In the process of tabletting the enteric-coated pellets comprising esomeprazole magnesium trihydrate,we found that adding glycerin monostearate and elevating the dose of triethyl citrate can significantly enhance the flexibility of enteric membrane.Simultaneously,elevating the rate of buffered excipient could minimize the damage of enteric membrane in the tabletting process.Finally,a multiparticulate tablet comprising enteric coated pellets of esomeprazole magnesium trihydrate was obtained with accumulative release higher than 90%at 45 min and acid resistance higher than 90%by using extrusion-spheronization and fluidized-bed coating as well as tabletting of pellets technology.Conclusion:The enteric-coated pellets comprising esomeprazole sodium or esomeprazole magnesium trihydrate we prepared had a quick in vitro release and good acid resistance.However,the stability of enteric-coated pellets comprising esomeprazole sodium is poorer than that of enteric-coated pellets comprising esomeprazole magnesium trihydrate.Therefore,esomeprazole magnesium trihydrate was more suitable to be made into enteric-coated pellets.By optimizing the coating prescription and preparation process,the enteric-coated pellets comprising esomeprazole magnesium trihydrate we prepared were suitable for tabletting.