Abstract

DEVELOPMENT AND EVALUATION OF FLOATING PULSATILE DRUG DELIVERY SYSTEM FOR CHRONOTHERAPY OF HYPERTENSION

Jumana K. K.*, Dr. Geetha V. S., Farsana T. and Mubashira N. P.

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Abstract

Ramipril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class II having a half-life of 2-4 hrs and 28-35% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crospovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer HPMC E5, HPMC E15, and HPMC K4M. The buoyant layer was optimized with HPMC K100M and sodium bicarbonate. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro drug release study. The superdisintgrant crospovidone showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The in vitro release profiles of Ramipril from pulsatile release tablets (PRT) prepared using HPMC K4M as retarding polymer were characterized by a predetermined lag time (5 hr), the duration of which depends on the kind and amount of the polymeric layer applied on the cores as well as type of superdisintegrant in core tablet. Floating pulsatile release tablets (FPRTs) were prepared by Central composite statistical design, in which the coating of core tablet with 240 mg of HPMC K4M and top coating of PRT with floating layer containing 80 mg HPMC K100M and 25 mg sodium bicarbonate provided desired lag time required for chronotherapy of hypertension. The developed system offers a simple and novel technique for pulsatile release of drugs. From the results it is concluded that the prepared PRT could achieve a rapid release after a lag time of 5h. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern.

Keywords: Floating, Press-coated, HPMC K100M, HPMC E5, HPMC E15, HPMC K4M, Pulsatile, Delivery.