(626h) Formulation for Weeklong Oral Drug Delivery in a Gastric Resident Oral Dosage Form

Patient adherence to medication regimens limits the effectiveness of treatments and adversely affects health outcomes in many disease areas. Long-acting oral therapies that can be infrequently dosed may improve adherence rates and pharmacokinetic profiles, leading to better patient outcomes. Multi-day oral drug delivery has recently been demonstrated in clinical trials using a unique gastric resident dosage form. The dosage form, which is administered inside a standard sized capsule, unfolds upon capsule disintegration into a flat star shape that physically resists passage out of the stomach. The controlled release formulation, composed of a drug-polymer blend with a thin polymeric coating, is formulated to achieve linear release over seven days and to resist burst release in the presence of food or ethanol. Formulations are manufactured using standard scalable unit operations including hot melt extrusion and pan coating. The formulation approach has been applied to the delivery of multiple small molecule drugs in preclinical models, including highly water-soluble compounds and poorly soluble compounds. Multi-day controlled release of the highly soluble drug memantine hydrochloride was demonstrated in human subjects in a single-dose clinical study. The gastric resident platform and formulation methodology may be applied to the delivery of a wide variety of drugs, which paves the way for future development of long acting oral products to benefit patients in many therapeutic areas.