Dextromethorphan hydrobromide (DXM) is a non-opioid antitussive agent with a short half-life (2–4 hours), a low therapeutic dose, and ionizable properties that make it suitable for formulation using ion-exchange techniques. However, information on its ion-exchange-based formulation remains limited. This study aimed to investigate the formation of DXM–resin complexes (DRC) using Tulsion® 344 resin, develop capsule dosage forms, and evaluate their drug release profiles. DRCs were prepared by stirring aqueous DXM solutions with the resin for 5 hours at drug-to-resin ratios of 1:3, 1:4, and 1:5. After drying, the complexes were encapsulated, characterized, and subjected to in vitro release studies in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Results showed increased DXM loading with higher resin ratios: 94.65% (1:3), 95.24% (1:4), and 96.18% (1:5). Correspondingly, drug release over 12 hours decreased as resin content increased: 66.25%, 56.72%, and 54.44%, respectively, compared to 101.06% for the immediate-release control. The 1:5 ratio provided the highest drug loading, and the capsule formulations met pharmacopeial requirements. The release kinetics of DXM from the capsules were consistent with the Higuchi diffusion model. |