Insertion of Dual Drugs of Hypertension in Gelatin Pockets for Chrono pharmacotherapy and its Evaluation by in-vitro and ex- vivo Studies

  Objective: The project was aimed to fabricate and evaluate a pulsatile capsule to program the release of dual antihypertensive drugs to mimic the circadian pattern of Blood Pressure. The formulation was optimized to repeatedly release the drug in pulses during the vulnerable period of 4 a.m. to noon upon administration during bed time. Methods: Formulation was prepared by means of Pulsincap technology. It consisted of an insoluble capsule body housing a layer of swellable polymer, a Losartan tablet sealed by an erodible polymer tablet. The system was capsulated in non-biodegradable body capped with water soluble cap containing fast releasing Amlodipine-sorbitol granules. The developed formulation was studied for physical characteristics, lag time determination, in vitro and ex vivo release. Results: The capsule cap dissolved in acidic pH released 99.29% of the amlodipine within 3h. The swellable polymer layer at the base of capsule pushed the plug along with losartan tablet out after a lag time of 6-7 h with 85.93% drug being released at the end of 12 h providing a time controlled need based release. Pulsincap formulated with Amlodipine-Sorbitol granules of G3 formulation, Losartan core tablet of C4 formulation and Erodible tablet of Guar gum with E4 formulation showed highest drug release over the period of 12 h and release was found to be followed Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of dual drugs is a suitable device for the time dependent and site specific delivery. Conclusion: This approach can be useful for the timed release of a combination antihypertensive medication and may provide effective 24 h control of Blood Pressure in hypertensive patients. The formulation was successfully designed to achieve enhanced bioavailability and dual pulsatile release. Bedtime dosing will more efficiently control the circadian spikes of hypertension in the morning.