Hydrophilic poly(urethanes) are an effective tool for gastric retention independent of drug release rate

Abstract Acyclovir is a poorly permeable, short half-life drug with poor colonic absorption, and current conventional controlled release formulations are unable to decrease the frequency of administration. We designed acyclovir dosage forms to be administered less frequently by being retained in the stomach and releasing drug over an extended duration. We developed a conventional modified-release matrix tablet to sustain the release of acyclovir and surrounded it with a hydrophilic poly(urethane) layer. When hydrated, the porous poly(urethane) swells to a size near or beyond that of the relaxed pylorus diameter and does not affect drug release rate. We demonstrated that the formulation is retained in the stomach for extended durations as it slowly releases drug, allowing for similar AUC but delayed tmax relative to a non-gastroretentive control tablet. Unlike many other gastroretentive formulations, this dosage form design decouples drug release rate from gastric retention time, allowing them to be modulated independently. It also effectively retains in the stomach regardless of prandial state, differentiating from other approaches. Our direct observation of excised rat stomachs allowed for a rigorous assessment of the impact of polymer swelling extent and prandial state on both the dosage form integrity and retention time.