Formulation and Evaluation of Gastro-retentive Floating Matrix Tablets of Lisinopril, Losartan, and Verapamil for Enhanced Gastric Retention and Controlled Antihypertensive Therapy

Abstract

Hypertension is a major global health concern and a significant risk factor for cardiovascular diseases such as stroke, myocardial infarction, and heart failure. Effective management of hypertension often requires long-term pharmacotherapy, and combination therapy using multiple antihypertensive agents has been widely recommended to achieve better blood pressure control. However, conventional oral dosage forms of antihypertensive drugs may exhibit short gastric residence time and variable bioavailability, leading to frequent dosing and reduced patient compliance. The present study aimed to develop gastro-retentive floating matrix tablets containing a combination of Lisinopril, Losartan, and Verapamil to enhance gastric retention and provide controlled drug release for prolonged antihypertensive therapy. Floating matrix tablets were formulated using hydrophilic polymers such as hydroxypropyl methylcellulose (HPMC), sodium alginate, and xanthan gum, along with sodium bicarbonate as a gas-generating agent. Preformulation studies including organoleptic evaluation, solubility analysis, melting point determination, and drug–excipient compatibility studies 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, and post-compression parameters including 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 (0.1N HCl). The optimized formulation exhibited a floating lag time of less than 60 seconds and remained buoyant for more than 12 hours, with sustained drug release extending up to 12–24 hours. Drug release kinetics indicated that the release followed the Korsmeyer–Peppas model, suggesting a diffusion-controlled mechanism. Stability studies conducted according to ICH guidelines demonstrated the stability of the optimized formulation. The developed gastro-retentive floating matrix tablets may offer improved gastric retention, enhanced bioavailability, and effective controlled antihypertensive therapy.