pH-dependent pulsatile delivery of Ambrisentan for the treatment of hypertension

Abstract

The greatest number of mortality in the world occurred due to hypertension. Several bodily functions are based on circadian rhythm including hypertension. The stimulation of the sympathetic nervous system in the early morning hours resulted in accelerating blood pressure which is a highly dangerous condition. This lead to cardiac failure and damage to the vital organs of the body. The current research focuses on pulsatile delivery of Ambrisentan for the treatment of high blood pressure which released the medicament at the right time and the right place. Primarily, core tablets were prepared with Ambrisentan. The compatibility of Ambrisentan with excipients was confirmed by FTIR analysis. The core tablets were evaluated for flowing characteristics which showed better flowing behavior and optimized core batch CT6 showed consolidation index 16.07±0.11 and angle of repose 27.02±0.14. Moreover, due to the least disintegration time (2.23±0.10) and greater dissolution release of 99.70 % ±0.49, CT6 was selected as an optimized core tablet for pulsatile delivery. Further, the combination of Eudragit L100 and ethyl cellulose were utilized for coating purposes in different proportion were utilized for achieving the desired lag time of 6 hrs. The optimized batch PC6 (Eudragit L100: EC 10) which comprised of 25:75 proportion showed a lag time of 6 hours, cumulative release of 99.25 % and content uniformity of 99.29±0.82. The dissolution release profile predicted zero-order release for Ambrisentan pulsatile tablets. The accelerated stability testing showed minimal loss of drug content when exposed at 40 0 C and 75 % relative humidity without altering lag time.