Studies On Sodium Rabeprazole Enteric Coated Pellets Tablet

Sodium Rabeprazole (SR) is the forth drug of new proton pump inhibitors on the market, which was developed after omeprazole, lansoprazole and pantoprazole. By inhibiting the activity of H+-K+-ATP enzymes on the gastric parietal cells, it can inhibit the excretion of gastric acid. SR is a kind of sodium salt, so its'aqueous solution is basic, which means that the SR solution is unstable in acid environment. Considering the physicochemical properties of SR, the physiological environment of the gastrointestinal tract and the compliance of the patients, the SR tablet was formulated from the SR enteric coated pellets, then the systematically study was carried out to evaluate the property of this formulation.Firstly, it was found that the maximum absorption wavelength of SR is 284 nm after scanning its ultraviolet spectra. Excellent linearity was found between concentration 224～1.074 mg/mL (r=0.9999) and the average recovery rate is 99.89%. The determination method of SR and related substances were also established, respectively, and it was found that these methods were accurate and reliable.Secondly, the tablets formulation from the SR enteric pellets was optimized by selecting suitable excipients such as antioxidants, pH regulators, lubricants and adhesives; the process parameters such as the compression pressure were also evaluated to obtain the high quality tablets. The optimal formulation and the preparation method were confirmed by Box-Behnken design (BBD) experimental model using appearance, content, dissolution and related substances of the preparations.Besides, the in vitro dissolution of the SR tablets was tested and the SR release behavior from the tablets fitted well to the first order kinetic model. Then the primary stability of the SR tablet was studied. Accelerated testing was carried out under temperature (40±2℃) and RH (75±5)% condition for 6 months. The results indicated that there was no significant difference between the data from the experimental group and control one. Then, the long-term stability of the SR tablets was studied under temperature (25±2)℃and RH (60±10%) condition for 12 months and no significant differences were found compared with the data from the zero month samples.Finally, the determination method of SR in the human plasm was established and the pharmacokinetic studies were carried out. The results indicated that, the Tmax of the experimental formulation and reference one (commercial formulations) were 104.90±1.59 and 88.72±0.89 min, respectively, the Cmax of were 3.37±0.042 and 2.33±0.053μg·mL-1, respectively. While, the AUC0-1 of which were 985.94±17.49 and 653.38±19.15μg-min·mL-1, respectively. There were no significant difference in bioavailability between the SR tablets and the commercial ones.