Development Of Rabeprazole Sodium Enteric Dry Suspension

Rabeprazole sodium is a novel proton pump inhibitor(PPI),and it is clinically used to treat diseases caused by excessive stomach acid,such as gastric and duodenal ulcers,esophageal reflux disease.Rabeprazole acts on four points of the H+/K+-ATP enzyme,as more binding sites.It has quick action,strongly inhibits gastric acid secretion,and has a large and sustained rise for the pH of stomach.As a newest PPI,rabeprazole sodium has higher pKa value than the first generation of PPIs,and the activated pH range is enlarged significantly,therefore,it accumulates more rapidly in the parietal cells and has more quickly effective and relieve than the first generation of PPIs.As rabeprazole sodium is unstable and easily be broken down in gastric acid,the commercial rabeprazole sodium products are enteric tablets and capsules.As special requirements of children,the aged and dysphagia,it needs to develop rabeprazole sodium enteric dry suspension in which the active pharmaceutical ingredient and excipients were made as granules by appropriate process,and it can be dispersed by adding water or other suitable liquid before application.The dosage form is convenience to special patients,and had great application prospect.(1)This paper investigated the physical properties including solubility,stability of active compound.The results showed that solubility of rabeprazole sodium decreased as the pH increases.The color of rabeprazole sodium will turn dark in light condition,and the impurities increased in high temperature condition.It is much hygroscopic in high humidity condition.(2)The main content of this paper is trying to apply the concept and principle of Quality by Design(QbD)to the design and experiment of the formulation of rabeprazole sodium enteric dry suspension.According to the guidance of QbD principle,critical quality attributes of products are determined based on the target product quality profile.Based on risk assessment of characteristics of raw materials and formulation composition,scientific and reasonable experimental was designed.(3)The quality standard of rabeprazole sodium enteric drying suspension was established.Meanwhile the methodological validation of related substances,content and drug release of the product was carried out to provide a scientific and effective analysis method for the detection of quality indexes affecting the effectiveness and safety of the product.Quality test results for rabeprazole sodium enteric-drying suspension was as follows:the drug content was 99.8%,single impurity was no more than 0.2%,total impurity was 0.52%,drug release was 95%(30min,75rpm),acid-resistance was 96%,and the settling volume ratio of prepared suspension was 1.01.(4)Using the established method of rabeprazole sodium enteric dry suspension,preliminary stability was investigated.It showed that the quality of rabeprazole sodium enteric dry suspension should be keep good in high temperature(60?),high humidity(75%RH),light condition and accelerate condition(40?,75%±5%RH).