The study aims to create a sustained release matrix tablet for Losartan potassium, an angiotensin II receptor antagonist, to improve patient compliance and maintain therapeutic blood or tissue levels for extended periods. The research investigates the role of novel semi-synthetic polymers and natural polymers in comparison to well-known release retarding agents. Gastroretentive drug delivery systems (GRDDS) are unique technologies designed to improve drug bioavailability and absorption by avoiding the first-pass effect. Losartan potassium, an angiotensin II receptor antagonist, has a bioavailability of 32% and a low elimination half-life, making it suitable for oral controlled release. The study utilized natural and synthetic polymers in matrix tablet preparation, concentration, drug particles size, additives, and excipients to modify drug release. The powder mixtures were tested for pre-compression parameters and post-compression parameters, and in-vitro dissolution studies showed good dissolution profiles for drug release. Formulations with higher concentrations and polymers sustained drug release for 24 hours. FT-IR Spectroscopy confirmed drug compatibility with polymers and other excipients