Date of Award
5-1-2026
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Micheal A. Repka
Second Advisor
Walt Chambliss
Third Advisor
Eman Ashour
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Poor aqueous solubility remains a key limitation in the oral delivery of poorly water-soluble drugs, particularly weakly acidic drugs such as ibuprofen, whose dissolution is highly pH dependent. This study aimed to develop a polymer-free, pH-modulating hot-melt extruded formulation of ibuprofen using excipient-driven alkalization to improve dissolution performance. Preliminary screening was performed to evaluate the pH-modulating and solubility-enhancing potential of magnesium oxide, meglumine, calcium carbonate, Neusilin, dicalcium phosphate, and sodium starch glycolate. Among these, sodium starch glycolate was additionally assessed for its role as a super-disintegrant to promote rapid disintegration of the extrudate contents upon capsule shell dissolution, thereby facilitating drug release into the dissolution medium. To facilitate rapid ma Magnesium oxide was selected as the primary alkalizing excipient based on its superior and consistent solubility enhancement in aqueous and acidic media, and a binary mixture of calcium carbonate and Neusilin in a 1:1 ratio as a diluent. A Box–Behnken design was then employed to optimize magnesium oxide-based formulations by investigating the effects of drug load, magnesium oxide amount, and sorbitol concentration on drug release, saturation solubility, and extrusion torque. Formulations were processed using hot-melt extrusion, and the extrudates were filled into hard gelatin capsules equivalent to 200 mg ibuprofen. The optimized formulation contained 60% w/w ibuprofen, 48.319 mg magnesium oxide, and 7.5% w/w sorbitol, with an overall desirability of 0.713. Compared with pure ibuprofen, the optimized formulation showed marked saturation solubility enhancement of ~106, ~28, ~70, and ~2.7 folds in water, pH 1.2 medium, pH 4.5 acetate buffer, and pH 7.2 phosphate buffer, respectively, along with improved dissolution across multiple media. Differential scanning calorimetry and powder X-ray diffraction indicated partial reduction in ibuprofen crystallinity, while Fourier-transform infrared spectroscopy confirmed chemical compatibility. Short-term accelerated stability at 40 °C/75% RH showed no detectable recrystallization or dissolution deterioration. These findings demonstrate the feasibility of magnesium oxide-based, polymer-free pH-modulating hot-melt extruded systems for improving dissolution of weakly acidic drugs.
Recommended Citation
Buha, Drashti Dineshbhai, "Enhancement of Ibuprofen Solubility Using pH-Modulation via Hot-Melt Extrusion" (2026). Electronic Theses and Dissertations. 8803.
https://egrove.olemiss.edu/etd/8803