Date of Award
5-1-2026
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Michael Repka
Second Advisor
Walter Chambliss
Third Advisor
Eman Ashour
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
The present study was designed to enhance the solubility and dissolution performance of febuxostat as a model drug by developing and optimizing a eutectic system for an oral solid dosage formulation via hot-melt extrusion (HME). Febuxostat, a poorly water-soluble drug, exhibits pH-dependent solubility, which limits its oral bioavailability. To address this challenge, a eutectic system was developed using choline chloride (hydrogen-bond acceptor) and urea (hydrogen-bond donor), thereby facilitating improved drug solubilization through intermolecular interactions. HME was utilized as a continuous processing approach to prepare and solidify the eutectic systems through their successful adsorption onto different carrier systems, including Ludiflash®, PROSOLV® SMCC, Neusilin® US2, and Aerosil® 200 Pharma. Furthermore, a design of experiments (DOE) approach was employed to systematically investigate and optimize the influence of drug loading, feed rate, and extrusion temperature on formulation performance. All the runs were successfully extruded and evaluated for their in-vitro drug release and solubility profiles. Through these DOE runs, an optimized formulation was obtained, which was further evaluated through in-vitro dissolution studies in multiple media (0.1 N HCl, pH 4.5 acetate buffer, water, and pH 6.8 phosphate buffer). This optimized formulation was subjected to solid-state characterization techniques, including DSC and FTIR, to confirm the presence of intermolecular interactions. Overall, the study demonstrates that integrating eutectic-based solubilization with hot melt extrusion provides an effective and novel approach to enhance the solubility and oral performance of poorly water-soluble drugs such as Febuxostat.
Recommended Citation
Nandvikar, Srushti Naresh, "Design and Development of Solvent-free Eutectic Systems-based Febuxostat for Solubility Enhancement through Hot Melt Extrusion" (2026). Electronic Theses and Dissertations. 8854.
https://egrove.olemiss.edu/etd/8854