DESIGN AND EVALUATION OF CHRONOTHERAPEUTIC ANTI-HYPERTENSIVE COMBINATION THERAPY USING MINI-TABLETS TECHNOLOGY

Hypertension or elevated blood pressure (BP) is a serious medical condition that significantly increases the risks of heart, kidney, brain, and other diseases. In persons with normal BP and uncomplicated essential hypertension, BP falls to the lowest levels during the nighttime sleep, and rises suddenly with morning awakening, and reaches the peak during the initial h of diurnal activity. The optimum therapy only results when the right amount of drug is delivered to the right targeted organ at the most suitable time. The present research aimed to develop a chronotherapeutic drug delivery system of combination drugs using mini-tablets technology, which can be administered at bedtime and releases Amlodipine within 2 h followed by the rapid release of Losartan after the lag time of 6 h. The developed mini-tablets were evaluated for compatibility studies, pre-and post-compression parameters. The compatibility studies indicate no chemical reaction, pre-compression parameters indicate good flow properties, and post-compression parameters were within limits. The obtained results of in-vitro studies have shown that Amlodipine and Losartan were not released simultaneously in 0.1N HCL (pH 1.2), as it is observed that only 9.76 ± 1.47 % of Losartan was released at the end of 6 h, which can be considered as lag time. Stability was also found for the developed mini-tablets-filled capsule formulation as per ICH guidelines. Thus, Amlodipine and Losartan can be used as combination products in the form of mini-tablets-filled-capsule formulation for the treatment of Hypertension.