The main pharmacological treatment for persistent gout and hyperuricemia is allopurinol, a xanthine oxidase inhibitor. However, patient adherence and therapeutic efficacy are seriously jeopardized by its quick gastrointestinal absorption, brief biological half-life (1-2 hours), and requirement for numerous daily doses. This review examines gastroretentive drug delivery systems (GRDDS) as a potential approach to increase drug residence time in the upper gastrointestinal tract, maximize absorption, enhance bioavailability, and lower dosing frequency to once daily. It also critically evaluates the pharmacokinetic limitations of traditional allopurinol formulations. Methods: PubMed, ScienceDirect, Google Scholar, and other pharmaceutical databases were searched for pertinent publications published between 2000 and 2024. Included were studies on the pharmacokinetics of allopurinol, gastroretentive technologies (such as floating, mucoadhesive, swelling, and magnetic systems), and the therapeutic implications of these technologies in gout treatment. Compared to immediate-release tablets, gastroretentive formulations of allopurinol showed lower Cmax with minimal peak-trough fluctuations, regulated plasma concentration profiles, extended stomach residence durations (8–12 hours), and enhanced bioavailability. Mucoadhesive microspheres, swellable polymer systems, and floating matrix tablets were shown to be the most promising platforms. In summary, GRDDS is a logical, evidence-based strategy to maximize allopurinol pharmacokinetics, allowing for once-daily dose that may greatly enhance patient adherence and treatment results in the treatment of chronic gout. Pharmacokinetic-pharmacodynamic modeling is required for additional clinical validation.

Keywords: Allopurinol, Gastroretentive Drug Delivery, Floating Tablets, Gout, Hyperuricemia, Pharmacokinetics, Xanthine Oxidase Inhibitor, Bioavailability Enhancement, Patient Compliance