Multiple Unit Particles System of Ramipril: An Approach to Enhance Stability

摘要

The present invention relates to produce multiple unit particle system (MUPS) of stabilized ramipril pellets, hydrochlorothiazide, diluents, superdisintegrants, and lubricants which produce better dissolution of the system for better bioavailability with improving stability and bioavailability of ramipril. More particularly, the present invention is directed for stabilized ramipril against decomposition into degradation products, namely ramipril-DKP and ramipril-diacid, during formulation and storage conditions. Simple ramipril formulation shows 15.15% related impurities after 3-month accelerated stability study, which was minimized to the 2.07% related impurities in ramipril pellets after 6 month accelerated stability study. By making MUPS of ramipril pellets, Hydrochlorothiazide and other excipients show better dissolution (100.4% of ramipril and 97.9% of hydrochlorothiazide within 60 min) to produce better bioavailability. So, making MUPS containing ramipril pellets with polymer coating and hydrochlorothiazide and other excipients shows better stability of ramipril along degradation and synergistic effect among hypertension in immediate delivery.