Preparation Of Rabeprazole Sodium For Injection

Rabeprazole is the most recently approved proton pump inhibitor, it is used for treating ulcers of the stomach and duodenum, erosive or ulcerative gastroesophageal reflux disease (GERD) and Zollinger-Ellison Syndrome. It also is used with antibiotics for eradicating Helicobacter pylori infections of the stomach that, along with acid, are responsible for many ulcers. There are tablets and capsules of Rabeprazole Sodium in market now, as we know, stimulating the mucosa of gastrointestinal tract, first-pass effect and bad absorbing are the shortcomings of these dosage forms. We prepared lyophilized injection of Rabeprazole Sodium which can settle the problems above, it is also usde for the patients who can't swallow.Several kinds of parameter were chosen to prepare lyophilized injection of Rabeprazole Sodium such as pH, solvent, Metal ions, xcipient and antioxidant according to the pH, characters and quantification. We find that the T_1/2 of Rabeprazole Sodium in different solvent as pH8, 9,10,11, 12 is 0.89, 27.32,100.44, 599.66 and 1503.65 hours. The pH is the most important item to the stability of Rabeprazole Sodium. When the pH between 11 to 12, it will be good. EDTA should not be put in because Metal ions made no effect to the stability of Rabeprazole Sodium. We chose Na₂SO₃ as antioxidant and mannitol as excipient. water is good for lyophilize and we use it as solvent. We designed the lyophilize curve after test the eutectic point. One blocks of freeze-dried Rabeprazole Sodium injection were produced. We investigated the stability of the preparation under the different storage situation, including strong light exposure for 10 days, high temperature acceleration at 60℃and 40℃for 10 days, high humidity exposure for 10 days. Conclusions showed the temperature and light had influence on the stability of Rabeprazole Sodium.We perform the quality analysis to the preparation, including its characters, identification, inspection, quantification, etc. We used high performance liquid chromatography (HPLC) method to perform quantification and related substance. When studying of methodology,the r of the linear regression is 1.0000, RSD is little than 0.2%, the recovery of the Rabeprazole Sodium is 100%. We inspected appearance, alkalinity, clarity and color of solution, water, heavy metal, arsenic, weight variation, particulate matter of the product and then established the quality standard of the freeze-dried Rabeprazole Sodium injection. According to this quality standard, we performed quality inspection to the preparations. And made conclusion that all items had measured up the demand.After storaged at 25℃and 6℃for 6 months. The stability of the preparation was evaluated from six aspects which are the appearance, pH, clarity and color of solution, particulate matter, quantification and related substance of preparations. Conclusions showed the stability of Rabeprazole Sodium was good and the technics is reasonable.Irritative, anaphylaxis and haemolyticus tests were performed to evaluate the injectable safety of Rabeprazole Sodium for injection. The results Showed the preparation had no hemolysis phenomenon when use the concentration of 0.5mg/ml, no significant irritation effect on vessels and no allergic response when use the concentration of 4mg/ml. The animal tests on safety provide a reliable basis for clinical application of Rabeprazole Sodium for injection.