FLOATING RANITIDINE MICROPARTICULATES: DEVELOPMENT AND IN VITRO EVALUATION

Objective: Rapid and inconsistent gastrointestinal tract (GIT) transit could result in reduced drug efficiency and the need for frequent dose administration, which usually result in patients’ incompliance. Ranitidine hydrochloride (RH), as a model drug is freely soluble, moisture sensitive drug with a short biological half-life (~2.5-3 h) and narrow absorption window in the initial part of the small intestine. The present study aimed to develop ranitidine floating multi-particulates (RFM) using melt granulation technique and investigation of the effect of lipids and additives on the physicochemical properties. Methods: RFM were prepared using Compritol ® 888 ATO, glyceryl behenate, Cutina ® HR, Cutina ® GMS, hydrogenated castor oil, glyceryl monostearate, and beeswax as lipids and ethyl cellulose, Povidone ® K 90 and Aerosil ® 200 as release modifiers. The effect of the preparation method and additives, as well as storage for 6 mo at 40 °C, on floating and release characteristics were evaluated. Results: Size distribution indicated that the prepared formulations exhibited reasonably small floating micro particulates; more than 90% of the prepared microparticles were less than 710 µm. Hausner ratios and Carr’s compressibility indices ranged from 1.17 to 1.29% and 14.54 to 22.4 %, respectively, and the angle of repose values was ≤40 °, indicating good flow properties. RFM containing Compritol ® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The tested additives (PVP, ethyl cellulose, Aerosil ® ) resulted in different degrees of retardation of drug release. The percent-floating of RFM was almost 100% in all formulations with the exception of formulations prepared using glyceryl monostearate. FT-IR and DSC studies indicated the compatibility of the excipients with RH. Stability results revealed an insignificant change in RFM properties over 6 mo. Conclusion: The prepared microparticles exhibited optimum particle size, good compressibility, and flow properties. RFM containing Compritol ® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The percent-floating of RFM was almost 100% in most formulations. FT-IR and DSC indicated good compatibility of the excipients with RH and insignificant change in RFM properties over 6 mo’s storage.