Development, optimization, and in vitro/in vivo evaluation of ranitidine hydrochloride resinate sustained release suspension

Abstract

Purpose: To prepare ranitidine hydrochloride (RH) sustained-release suspension aimed at improving its safety, effectiveness and convenience of administration. Methods: The RH resinate suspension was prepared using bath method, with a cation- exchange resin as carrier. To obtain an ideal sustained release effect, RH resinates were coated with Eudragit®RS100 using the surface coating method, followed by optimization through a single-factor experiment and response surface analysis. The optimized RH suspension was characterized using accelerated stability test. Moreover, it was pharmacokinetically evaluated in vivo. Results: The optimized RH resin microcapsules showed relative mean deviation between the predicted and measured release values that was < 10 %, (p < 0.05) and demonstrated good reproducibility. Accelerated stability test results showed that the optimized RH suspension exhibited good stability over a period of 6 months (F > 0.9; drug content: 97 – 100 %, drug release: f2 > 50; drug leakage < 0.5 %), with good redispersibility. Results from pharmacokinetics showed that values of Tmax for RH sustained-release suspension and RH common tablet were 4.00 and 2.5 h, respectively (p < 0.05), while the corresponding Cmax values were 2545.78 and 3245.97 ng/mL, respectively (p < 0.05). Results of analysis of AUC0-24 showed that they were equivalent in terms of AUC0-24 (p < 0.05) and bioavailability of 101.05%. Conclusion: The optimized ranitidine hydrochloride (RH) sustained-release suspension has been successfully prepared using ion-exchange resin as a carrier and Eudragit® RS100 as a coating material.