Purpose <p>The study intended to develop and investigate controlled release non-effervescent floating polymeric tablets of Clarithromycin and Pantoprazole to enhance their bioavailability by prolonging the gastrointestinal transit time of drugs, a system for Helicobacter pylori elimination.</p> Methods <p>The gastro-retentive tablets were prepared via direct compression method using different concentrations and combinations of hydroxypropyl methylcellulose (HPMC) K4M, Carbopol and guar gum as hydrophilic polymers and Avicel 102 as a filler. The pre-compression solid mixture was characterized for angle of repose and compressibility index, applying Hausner’s ratio to predict the flowability, as well as fourier transform infrared spectroscopy for drug-excipient interaction evaluation. The prepared tablets were investigated for dimension, hardness and friability, weight variation and content uniformity, swelling index, density, buoyancy and in-vitro drug release.</p> Results <p>All the formulations exhibited desired floating and flow attributes. Solid-state characterization revealed no chemical interaction between excipients and the drugs. With reference to in-vitro study results, all formulations, except F7, have displayed slow drug release and reduced burst effect (F6). The lowest lag buoyancy of 5&#xa0;min was achieved in F2. This study develops a non-effervescent floating system for dual drug delivery to enhance gastric residence time, thereby optimizing local therapeutic effects. This innovative approach aims to reduce dosing frequency and associated side effects, improving patient compliance and treatment efficacy for gastric ulcer. This innovative approach can provide effective ulcer healing with shortened treatment time, reduced side effects and improved patient compliance.</p> Conclusion <p>This study also highlights the effectiveness of non-effervescent approach to improve dissolution and bioavailability.</p> Graphical Abstract <p></p>