| Proton pump inhibitor(PPI) is one of the benzene and imidazole derivatives, which significantly improves the treatments of the acid-related diseases. With the increase of both the reflux diseases and the acid-secretion-related gastrointestinal diseases, the demand for proton pump inhibitors(PPIs) will still continue. Omeprazole is the benzene and imidazole proton pump inhibitor that was firstly used for the clinical purpose. Omeprazole has been on the market for many years, and its mature synthesis process, low impurity and high yield rate can provide the cheap and stable raw materials for the manufacture of omeprazole preparations.There are two kinds of forms of the omeprazole preparations, i.e. the solid forms for the oral administration, which include omeprazole enteric-coated tablets and omeprazole enteric capsules, and the injection preparations, which include omeprazole sodium for injections(Lyophilized Powder). There are some shortcomings with the traditional omeprazole oral preparations. Omeprazole is not stable in acid environment but easily degradable in the gastric fluid. So, in the enteric-coated preparation, the omeprazole is segregated from the gastric fluid by using the enteric polymer materials with the good film forming property. The enteric materials are not dissolved in the acid but in the intestinal fluid, which therefore protects the omeprazole. The enteric coating technology is of high requirements and increases the cost of materials and labors. There often are the adhesion phenomenon and humidity sensitivity with the coating. And there is a delay with the peak time of the enteric-coated preparation.Because omeprazole is unstable in the acid environment, it can be fast degraded in the gastric acid. Compound omeprazole capsule is a compound preparation of the omeprazole and the sodium bicarbonate, which are mixed together directly and then filled into capsule, so in expectation that, after the capsule is taken orally, the sodium bicarbonate is released rapidly neutralizes gastric acid, takes the anti-acid effect, and simultaneously provide omeprazole with stable environment. It makes the omeprazole and sodium bicarbonate be released in the stomach at the same time. However, since it is only a simple mixture of the omeprazole, sodium bicarbonate and excipient material, the order of disintegration cannot be obtained accurately. This article aims at making a kind of compound omeprazole fast-released tablet on basis of the compound omeprazole capsule, i.e. the compound omeprazole core encapsulating tablets, a kind of tablet which is packaged with another medicinal powder chip between two medicinal powder layers.This article studies and develops a kind of core encapsulating tablets with the active constituents of omeprazole and sodium bicarbonate, and the outer layer whereof is the sodium bicarbonate which can be disintegrated rapidly, preventing the omeprazole from the contact with gastric acid and degradation in the gastric acid. After the disintegration of outer layer of sodium bicarbonate, omeprazole will be rapidly disintegrated and dissolved in the stomach. Omeprazole inhibits the gastric acid secretion.The manufacture of the compound omeprazole core encapsulating tablets is divided into three steps: one is the manufacture of the core, the second the outer layer and the third the core encapsulating tablet. Firstly, the single factor test is carried out for the prescription of core: the study of the dosage of stabilizer and the dosage of disintegration agent, i.e. the prescription and process technology of the core of omeprazole tablets to be determined, regarding the particle size, angle of repose, disintegration time and dissolution rate as the indicators of study. For the outer layer, the powder direct mixture is adopted, and the dosage of disintegration agent is studied, the prescription and process technology of outer layer is determined by testing the angle of repose, disintegration time and hardness.The contemplated test in vitro, i.e. the test of the manufactured samples and the currently commercialized products in term of the acid endurance and acid proof, bring a result that the dissolution rate of the self-manufactured samples is higher the relevant substance is slightly lower than those of the currently commercialized products, which means the products are more stable in the gastric fluid. The content, relevant substances and dissolution of the omeprazole, which are tested with the HPLC method, and the contents of sodium bicarbonate, which are tested with the titration method, all confirm to the requirements of quality standards. The tests of the related substances, dissolution andcontent, and the test of the content of sodium bicarbonate, both under the circumstance that the samples are placed in the conditions high temperature(60°C), light, high humidity(75%±5%) for stress testing, bring a result that the self-manufactured omeprazole sample is more stable than the compound omeprazole capsules currently sold on the market. On this basis, the stability of the preparation is evaluated by determining the prescription and process technology and technology roadmap, carrying out the pilot magnification of the samples according to the approved prescription, and carrying out the accelerated test(40℃±2℃,RH75%±5%) and long-term test(25°C±2°C,RH60%±10%) with the magnified samples. |
