Solid-solution fibrous dosage forms for immediate delivery of sparingly-soluble drugs: Part 2. 3D-micro-patterned dosage forms

Abstract

In part 1, we have investigated drug release by solid-solution single fibers comprising a sparingly water-soluble drug (ibuprofen) and a highly water-soluble dual excipient (low-molecular-weight hydroxypropyl methyl cellulose (HPMC) and polyoxyl stearate (POS)). In this part, fibrous dosage forms of the same formulation are prepared by 3D-micro-patterning, tested, and modeled. Upon immersion in a small volume of dissolution fluid, the dosage forms rapidly swelled and formed a low-viscosity medium, which subsequently dissolved. The dissolution time increased slightly with volume fraction of the fibers, φs, in the solid dosage form, but was less than 25 minutes even up to φs = 0.65. After dosage form dissolution, the fluid was supersaturated by a factor of two; the drug concentration then gradually decreased to solubility. The solubility was proportional to the concentration of POS, and was enhanced by a factor of six at φs = 0.65 (the most densely-packed dosage form). Theoretical models suggest that the dissolution fluid percolates the contiguous void space almost immediately, and the HPMC-POS fibers expand isotropically as water diffuses in. Because the void space remains contiguous in isotropic expansion, the dissolution fluid continues to percolate through and diffuse into the fibers. Thus, even the densely-packed dosage forms form a low-viscosity medium that deforms and dissolves rapidly. Consequently, the solid-solution fibrous dosage forms enable enhanced release rate, supersaturation, and solubility of sparingly-soluble drugs.