Search

Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.

Early morning hypertension and a high heart rate are risk factors for cardiovascular disease. The DOHSAM study was designed to evaluate the effect of candesartan on early morning blood pressure (BP) and heart rate in hypertensives. We used a prospective, randomized, open-label design. Protocol 1: Patients with early morning BP more than 135/85 mmHg who were not on any antihypertensive drug or on candesartan were given amlodipine 2.5 mg/day (amlodipine group, n = 22) or added candesartan 4 mg/day (candesartan group, n = 36). Candesartan or amlodipine was added when BP did not fall lower than 135/85 mmHg. Protocol 2: Early morning hypertensives who were on other angiotensin receptor blockers (ARBs) ( n = 50) such as valsartan, losartan, telmisartan and olmesartan were switched to candesartan. Early morning BP significantly decreased in the candesartan group compared with the amlodipine group 9 and 12 months after treatment. Switching other ARBs except for olmesartan to candesartan significantly decreased early morning systolic and diastolic BP 3, 6, 9 and 12 months after treatment. Heart rate in the office significantly decreased by switching to candesartan 6, 9 and 12 months after treatment. In conclusion, candesartan significantly decreased early morning hypertension more than amlodipine or other ARBs except olmesartan in early morning hypertensives. [ABSTRACT FROM AUTHOR]