Expandable fibrous dosage forms for prolonged drug delivery

摘要

Many drug therapies could be greatly improved by dosage forms that reside in the stomach for prolonged time and release the drug slowly. In this work, therefore, slow-release fibrous dosage forms that expand rapidly in the gastric fluid to prevent their passage into the intestines are investigated. The dosage forms consisted of acetaminophen drug and a high-molecular-weight hydroxypropyl methyl cellulose (HPMC) excipient. Upon immersion in a dissolution fluid, they transitioned to viscous, and expanded in proportion to the square-root of time and the reciprocal of fiber radius. The normalized axial expansion was up to 100 percent by fifteen minutes, fast enough to convert a swallowable, 10-mm diameter disk into a gastroretentive, 20-mm diameter viscous gel. The drug was released slowly, eighty percent in 2-8.4 hours. Theoretical models show that the fibrous dosage forms expand rapidly due to the fast diffusion of dissolution fluid into the thin fibers. The fibers then coalesce into a uniform viscous gel, and the diffusion length increases from the radius of the thin fibers to the half-thickness of the gelated dosage form. Consequently, drug diffusion out is slow, and the twin requirements, fast expansion and prolonged drug release, are simultaneously satisfied.