Solid-solution fibrous dosage forms for immediate delivery of sparingly-soluble drugs: Part 1. Single fibers

Solid solutions of sparingly water-soluble drugs and highly water-soluble excipients are widely used for enhancing the drug delivery rate into the blood stream. The basic physico-chemical mechanisms, however, are not well understood. To delineate the mechanisms, therefore, in this work solid-solution fibers are immersed in a small volume of dissolution fluid and the drug concentration is monitored versus time. Two formulations are considered: ibuprofen drug and low-molecular-weight hydroxypropyl methyl cellulose (HPMC) excipient; and ibuprofen and HPMC and polyoxyl stearate (POS) excipients. The fibers dissolved in the dissolution fluid and the drug was released up to three orders of magnitude faster than by ibuprofen particles, yielding a maximum supersaturation in the fluid up to 6.5 in 10-15 minutes. Past the maximum, when the fiber was fully dissolved, the drug concentration gradually decreased to terminal solubility, up to a factor of 10 greater than that of pure ibuprofen. Models suggest that the drug release rate is proportional to the drug concentration at the fiber-fluid interface, which is enhanced due to both supersaturation and solubility-increase. The interface supersaturates because the drug-molecule release rate from the fast-eroding HPMC fibers is greater than the precipitation rate within; the solubility increases proportionally to the concentration of micelle-forming POS. Similarly, the dissolution fluid supersaturates, and due to the presence of POS in the solution the terminal solubility is increased. Thus the solid-solution fibers with dual, low-molecular-weight HPMC-POS excipient enhance the release rate, supersaturation, and solubility of sparingly-soluble drugs, and their delivery rate into the blood stream.