Advances in biopolymer-based floating raft drug delivery systems for gastroretentive therapy

The efficient gastric absorption of orally administered drugs showing pH-dependent solubility, narrow absorption windows, or localized gastric action remains a critical challenge. Conventional immediate-release and sustained-release dosage forms often result in poor bioavailability, fluctuating plasma drug levels, and increased dosing frequency due to rapid gastric emptying and variable gastrointestinal transit. Presently, expandable, high-density, and mucoadhesive systems represent the most widely investigated gastroretentive approaches; unfortunately, these systems have exhibited limited clinical outcomes because of formulation complexity and unacceptably variable gastric retention. FRDDS represents a promising clinically relevant strategy that overcomes such limitations <i>via</i> the formation of low-density buoyant gel structures that can reside in the stomach for prolonged periods. Maintenance of the drug in the gastric milieu by FRDDS enhances dissolution under acidic conditions, allowing for controlled and site-specific drug release and improving therapeutic efficacy while reducing dosing frequency. This review provides a critical evaluation of recent advances in FRDDS, focusing on mechanisms of raft formation, gastroretentive performance, formulation strategies, and their clinical applicability. Inter-individual variability in the gastric environment, fed-fasted effects, and translational limitations are discussed as key challenges. Overall, FRDDS embodies a robust and versatile gastroretentive platform with significant potential to improve oral drug therapy in chronic, infectious, and gastric-related diseases.