Study On The Quality Standards Of Omeprazole/Sodium Bicarbonate Powder For Oral Suspension

Omeprazole, the frist proton pump inhibitors(PPIs) used in clinical practice, could effectively interact with the final step of the gastric secretion, which relieves the symptoms and prevents complications associated with acid-related conditions. Compared to H2-receptor antagonists, omeprazole yields faster healing and it is often prescribed to treat peptic ulcer disease, gastroesophageal reflux disease. Over two decades of clinical use have demonstrated that the safety and efficacy of omeprazole are comparable to other PPIs, such as lansoprazole, pantoprazole, etc. Omeprazole/sodium bicarbonate powder for oral suspension, which is not yet on sale in China, is considered as a kind of generic drugs. Unlike the enteric-coated preparations, this formulation is convenient for pediatric patients or a patient population which has difficulty in swallowing.Since the quality standards for omeprazole/sodium bicarbonate powder for oral suspension have not been recorded by the Pharmacopoeias of the United States, Britain and some other countries, this dissertation focus on the establishment of quality criteria for controlling the quality of omeprazole/sodium bicarbonate powder for oral suspension. We have reported a sensitive HPLC method for determination of the related substances in both the test and the reference products. Effective chromatographic separation was achieved on a Kromasil C8 column with a mobile phase of pH 7.6 phosphate buffer: acetonitrile(75:25, v/v). The samples were subjected to hydrolysis(acidic, alkaline), photolysis, thermolysis and oxidation. Resolution between omeprazole and its impurities was found to be larger than 2.0. Validation parameters, such as system suitability, linearity, precision, accuracy and robustness showed results within the acceptable criteria. Besides, a HPLC method for quatitative detection of omeprazole and an acid-base titration procedure for analyzing sodium bicarbonate were developed, respectively. The contents of both omeprazole and sodium bicarbonate in test products were found to be in the range of 95 % to 105 %.In order to discriminate the particle size of omeprazole and to estimate the dissolution performance of the products, a dissolution method using pH 7.4 phosphate buffer in a dissolution apparatus equipped with paddles(speed 50 rpm) was selected. The dissolution data indicated that the test samples were consistent with the reference formulation by using the dissolution curve. Acid resistance assessment revealed that the pH values of gastric fluid would increase rapidly due to the presence of sodium bicarbonate, thus preventing omeprazole from being destroyed. The test products were proved to be stable after 6 months of accelerated test and 24 months of long-term test.At present, the Chinese State Food and Drug Administration is launching a quality consistency evaluation for generic drugs. Improving the quality standards of generic drugs plays an important role in ensuring the safety of drug use in public. The evaluation of the test products, including related substances, content, dissolution and acid resistance, showed that all the results were consistent with the reference products.