Preparation And Quality Study Of Omeprazole Pulsatile Pellets

Omeprazole is one of Proton Pump Inhibitors(PPIs), which can inhibit gastric acid secretion of gastric parietal cells. It can be used in treatment of peptic ulcer, gastroesophageal reflux disease and Zollinger-Ellison syndrome. However, there are some shortcomings of omeprazole such as short half life, inhibiting gastric acid secretion incompletely, and nocturnal acid breakthrough can be observed sometimes while using it. In this study, omeprazole enteric-coated pulsatile pellets were prepared. The pellets could release omeprazole twice at different points in intestine after oral administration, so they can inhibit gastric acid secretion more thoroughly and improve efficacy as the result.In this study, the cores of pellets, which contained omeprazole, were prepared by extrusion-spheronization at first. At the same time, the measuring methods of content of omeprazole and drug release rate were developed according to Chinese Pharmacopoeia. The composition of formulation and preparing technique were screened and optimized by using yield of cores with particle size between 16 to 24 mesh, omeprazole content, and release rate in phosphate buffer(pH6.8) as index. The optimal formulation of pellet cores contained 20% of omeprazole, 30% of MCC, 20% of mannitol, 10% of Na2CO3, and 20% of PVPP XL-10. The process was as followed: mixed omeprazole and excipients, added 8% of HPMC E5 solution with H2O-EtOH(90:10, w/w) into the mixture of powder to prepare wet mass, extruded the wet mass with the extrusion velocity of 30r/min, shaped it with spheronization velocity of 1300r/min(1min) and then 1000r/min(3min) to prepare pellet cores, dried the cores at 35~40℃(2h), screened cores to get cores with particle size between 16 to 24 mesh.Coated the cores with 8% of Opadry(gastric) solution as isolated layer. Optimized technique according to content of omeprazole of pellets after coated isolated layer, and determined weight gain of isolated layer using content of omeprazole after coated enteric layer as index. The technique parameters was as followed: spheronization velocity was 150 r/min, inlet air temperature was 40~45℃, inlet and exhaust air speed was 1200r/min, pressure of atomization was 0.14 MPa, flowing rate of coating fluid was 3g/min, weight gain was 8%.Coated the pellets with enteric layer using A. 10% Opadry(enteric,94 Series) solution and B. 11% Eudragit S100 solution separately to prepare enteric-coated pellets. Optimized technique and determined weight gain of enteric layer according to content of omeprazole after the test of acid-proof. The technique parameters was as followed: spheronization velocity was 150 r/min, inlet air temperature was 40~45℃, inlet and exhaust air speed was 800r/min, pressure of atomization was 0.08 MPa, and A. flowing rate of coating fluid was 3g/min, weight gain was 25%; while B. flowing rate of coating fluid was 2.6g/min, weight gain was 30%.Packed the two kinds of omeprazole enteric pellets in capsules in accordance with A and B in a ratio of 1 to 3. The omeprazole content of the pellets in capsules was 97%. Then measured release rate of capsules in pH6.8 and 8.0 phosphate buffer. In pH6.8, the release rate was 30% at 60 min and 90% at 120min; while in pH8.0, the release rate was 80% at 60 min and 90% at 120 min. The stress test and initial stability test showed the omeprazole enteric-coated pellets were stable。...