Preparation And Quality Control Of Esomeprazole Magnesium Enteric-coated Pellets

Esomeprazole magnesium, the S-isomer of omeprazole, is the first left-hand proton pump inhibitor. It is widely used for the treatment of acid related diseases such as gastro-esophageal reflux disease, peptic ulcers. However, esomeprazole magnesium has the chemical structure of sulfonyl benzimidazole which is easy to degrade under acidic conditions, causing the reducing of content and the increasing of related substance, resulting in the reducing of curative effect. Considering the physicochemical properties of esomeprazole magnesium, the physiological environment of the gastrointestinal tract and the compliance of the patients, researchers often prepare esomeprazole magnesium enteric-coated pellets. We prepared esomeprazole magnesium enteric-coated pellets by bottom spray fluid bed coating technology, investigated the formulation, and then carried out a systematically study to evaluate its quality control methods.Firstly, we prepared esomeprazole magnesium enteric-coated pellets from pill core, and then investigated the parameters of fluidized bed by taking the coating efficiency, the fluidized state of coating process as index. We added the alkaline layer to ensure the stability of the enteric-coated pellets. The weight gain of enteric layer, the content of adhesive and solubilizer in drug layer were also evaluated with the acid resistance and dissolution of pellets as the index. Through screening, we got an optimal formulation:the drug layer:HPMC-E5:Tween-80:purified water:esomeprazole magnesium=2:0.5:97.5:10, the weight of coating was 100%; the basic layer: HPMC-E5:talcum powder:purified water =7:3:140, 0.2 mol·L-1NaOH solution was used to adjust pH to 10.0, the weight of coating was 20%; the neutral layer: HPMC-E5:talcum powder:purified water =15:11:274, the weight of coating was 25%; the enteric layer: EudragitL30D-55:Tween-80:TEC:purified water=150:1:4:345, the weight of coating was 80%; the protective layer: HPC-SL:PEG-4000: purified water =2:10:89, the weight of coating was 6%~8%.Secondly, the measured method of content, release and related substances for esomeprazole magnesium enteric-coated pellets were established, followed by a systematically validation. The results showed that the linear range, the precision, accurency and durability met the requirements well, providing a effective method for the quality control of esomeprazole magnesium enteric-coated pellets.Lastly, the properties of pellets made by the optimized formulations were evaluated and the dissolution curves of the optimized formulations and the marketed products were compared. The content, related substances, acid resistance and content uniformity of the optimized formulations were all complied with the requirements. Through calculation, the similarity factor f2 of release curve between the optimized formulations and the marketed products was more than 50, indicating that their release curves were similar.We studied the primary stability of esomeprazole magnesium enteric-coated pellets of the optimized formulations. Accelerated testing was carried out under temperature(40±2) ? and RH(75±5)% condition for 6 months, and long-term testing was carried out under temperature(25±2)? and RH(60±10)%condition for 6 months. The results indicated that there was no significant difference between the experimental group and control ones. Results demonstrated that the quality of esomeprazole magnesium enteric-coated pellets was reliable and it had favourable application value.