Review Article GASTRORETENTIVE EFFERVESCENT FLOATING TABLETS (GREFT) OF DRUGS ACTING ON CARDIOVASCULAR DISEASES SUTAPA BISWAS MAJEE * , TRISHA MISHRA, SOUVIK GUPTI Division of Pharmaceutics, Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata-Group of Institutions, 60 B l Saha Road, Kolkata-700053, India * Corresponding author: Sutapa Biswas Majee; * Email: sutapabiswas2001@yahoo.co.in Received: 18 Apr 2024, Revised and Accepted: 20 May 2024 ABSTRACT Incidences of Cardio Vascular Diseases (CVDs) are increasing in an alarming proportion in India. Conventional oral dosage forms cannot be retained in the stomach for long owing to gastric emptying. Moreover, drugs which are commonly employed in management of chronic CVDs either have reduced solubility at alkaline pH, undergo colonic degradation, exhibit site-specific absorption or varying bioavailability with combination therapy. Gastro-retentive drug delivery systems (GRDDS) are designed to overcome these challenges. Since 2006, Food and Drug Administration has approved only few GRDDS for treating CVDs. The aim of the present review is to summarize the outcomes of research carried on GRRDS with drugs for CVDs since last 15 y and comprehensive analysis of limitations of such studies due to which no product has been approved or commercialized in over last 18 y. Literature survey includes single unit, multi-particulate, monolayer and bilayer dosage forms with or without effervescence-inducing agents and made of natural and/or synthetic polymers like hydroxypropylmethyl cellulose, natural gums etc. Efforts have been made to compile in vitro buoyancy data such as floating lag time, total floating time, swelling index, release profile and release kinetics. Among various studies reported on monolayer and bilayer Gastro-Retentive Effervescent Floating Tablets, only 3 involved bioavailability studies in human volunteers. Toxicity studies in animals or stability studies are totally lacking. Observation with floating-type multi-particulate GRDDS is more disappointing. lack of safety, efficacy data, stability data, in vivo imaging studies and in vitro-in vivo correlation data might be actually responsible for lack of commercialization of any GRDDS for drugs acting on CVDs in 21 st century. Keywords: Bilayer tablet, Buoyancy, Cardiovascular diseases (CVDs), Effervescent floating, Floating lag time, Gastro retentive drug delivery systems (GRDDS), Gums, Hydroxypropylmethyl cellulose, Multi-particulate, etc © 2024 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijpps.2024v16i7.51296 Journal homepage: https://innovareacademics.in/journals/index.php/ijpps INTRODUCTION In 2023, more than 600 million people worldwide are reported to be affected with Cardio Vascular Diseases (CVDs). It is estimated that the number of adults in the United States with symptoms of CVDs who are 25 years of age or older will increase by almost 19% from 2012 till 2030. In 2021, 10.8 million deaths were caused by hypertension. Up to 76 million mortalities can be avoided globally between 2023 and 2050 if suitable measures and precautions are adopted. CVDs have emerged as India's major cause of death since the turn of the century, leaving behind malnutrition-related diseases, diseases affecting mother and neonates, tropical infectious and communicable diseases. It is alarming that Indian population is at a higher risk of CVDs compared to the rest of the world, and they are affected by CVDs at least ten years earlier and during peak of their career than persons of European origin [1-4]. Conventional orally administered dosage forms fail to remain in the gastrointestinal tract (GIT) for a sufficient period of time to exert prolonged therapeutic action mainly due to their passage out of the stomach through pyloric sphincter by intrinsic peristaltic movement within maximum 4 h (fed stomach). Gastric retention period can be greatly enhanced by designing appropriate gastro-retentive devices, with an aim of maximizing drug’s bioavailability and minimizing wastage of active pharmaceutical ingredient. Gastro-retentive drug delivery systems (GRDDS) are very suitable for drugs that are degraded in the alkaline pH of the intestines or rendered insoluble or are precipitated at intestinal pH or for drugs having their absorption window in the stomach or meant specifically to treat pathological condition of the stomach itself [5-8]. Advantages of GRDDS as drug delivery systems 1. Significant improvement in the bioavailability with drugs which are absorbed from upper GIT. 2. Reduced frequency of administration with drugs having short elimination half-life, thereby ensuring patient compliance. 3. Minimizing fluctuations in plasma concentration level and achieving ideal steady state for better management of chronic conditions. 4. Reduced risk of toxicities and adverse effects [9-13]. Some of the drugs which are commonly employed in management of chronic CVDs suffer from issues like reduced solubility at alkaline pH (metoprolol, propranolol, verapamil, diltiazem), degradation in colonic environment (captopril), exhibiting site-specific absorption from upper GIT (frusemide) and varying rate and extent of bioavailability with combination therapy. Till date, only few GRDDS are commercially available with drugs for different arms of CVDs (table 1). Table 1: Marketed GRDDS of drugs acting on CVDs Drug Indication Brand name Manufacturer FDA approval in Reference Carvedilol Hypertension, heart failure and heart attack Coreg CR® Glaxosmithkline, USA 2006 [14] Prazosin Hypertension Prazopress XL® Sun Pharma, India 1992 [14] Verapamil HCl Angina, unstable angina, hypertension, paroxysmal supraventricular tachycardia (PSVT) prophylaxis, and supraventricular tachycardia (SVT). Covera HS® DURECT Corporation, USA 1998 [14] Nisoldipine Arterial hypertension Sular® Skyepharma, Shionogi Pharma Inc. UK 1995 [14] International Journal of Pharmacy and Pharmaceutical Sciences Print ISSN: 2656-0097 | Online ISSN: 0975-1491 Vol 16, Issue 7, 2024