Expandable, dual-excipient fibrous dosage forms for prolonged delivery of sparingly-soluble drugs

Abstract

In this work, expandable fibrous dosage forms containing water-absorbing and fiber-strengthening excipients are investigated for prolonged delivery of sparingly-soluble drugs. The formulation comprised: sparingly-soluble ibuprofen drug; water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) excipient; and strengthening methacrylic acid-ethyl acrylate excipient. Upon immersion in a dissolution fluid, the single fibers and all the dosage forms (fiber volume fractions, φ = 0.16, 0.39, and 0.56) expanded roughly at the same rate. The size of the dosage forms doubled in fifteen minutes, and they were converted into a highly viscous gel. The gel was stabilized by the strengthening excipient for over two days. Eighty percent of the drug was released from single fibers in less than an hour, and in thirty-eight hours from the dosage form with φ = 0.56. Theoretical models suggest that if φ is small, drug release is limited by the diffusion of drug molecules through the thin fibers, which is fast. If φ is large, however, drug release is limited by the diffusion of drug molecules through the thick, monolithic dosage form gel, which is slow. Between these extremes, the drug release time increases exponentially with φ.