Development and Optimization of a Triple-Drug Gastroretentive Drug Delivery System Containing Lisinopril, Losartan, And Verapamil Using Hydrophilic Polymer Matrix Technology

Abstract

Hypertension is a major global health concern that often requires combination therapy for effective blood pressure control. Conventional oral dosage forms of antihypertensive drugs frequently exhibit short gastric residence time and variable bioavailability, which may reduce therapeutic efficacy and patient compliance. The present study aimed to develop and optimize a gastroretentive floating matrix tablet containing a combination of Lisinopril, Losartan potassium, and Verapamil hydrochloride using hydrophilic polymer matrix technology. Floating tablets were formulated using hydroxypropyl methylcellulose (HPMC K100M), sodium alginate, and xanthan gum as matrix-forming polymers, while sodium bicarbonate and citric acid were used as gas-generating agents. Preformulation studies including organoleptic evaluation, melting point determination, solubility studies, and drug–excipient compatibility (FTIR and DSC) were performed. The prepared formulations were evaluated for pre-compression parameters such as angle of repose, bulk density, tapped density, Carr’s index, and Hausner ratio. Post-compression evaluation included weight variation, hardness, friability, drug content uniformity, floating lag time, total floating duration, swelling index, and in-vitro drug release. Dissolution studies were carried out using USP dissolution apparatus II in simulated gastric fluid (0.1 N HCl). The optimized formulation showed floating lag time below 60 seconds and remained buoyant for more than 16 hours. In-vitro dissolution studies demonstrated sustained drug release up to 12 hours. Drug release kinetics followed the Korsmeyer–Peppas model, indicating diffusion-controlled drug release from the polymer matrix. Stability studies conducted according to ICH guidelines confirmed that the optimized formulation remained stable under accelerated storage conditions. The developed gastroretentive system demonstrated potential for improving gastric retention, enhancing drug bioavailability, and providing controlled antihypertensive therapy.