Novel Hybrid Polymer-Lipid-Based Formulations for Enhanced Dissolution Rates of Poorly Water-Soluble Drugs: A Quality by Design (QbD) Approach via Hot Melt Extrusion.

This study presents a Quality by Design (QbD) strategy combined with Design of Experiments (DoE) to develop hybrid polymer-lipid hot-melt extruded (HME) formulations aimed at improving the dissolution rate and palatability of ibuprofen (IBU), a Biopharmaceutics Classification System (BCS) Class II drug with poor aqueous solubility. A fractional factorial design was applied to evaluate the influence of Eudragit EPO and Gelucire 48/16 (GLC) ratios on the preparation of IBU-loaded extrudates. Physicochemical characterisation of the micronised extrudates, using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), confirmed the formation of amorphous solid dispersions (98.0-99.8%). The DoE analysis demonstrated that the EPO/GLC ratio significantly affected crystallinity, particle size distribution, and dissolution performance. The optimised hybrid polymer-lipid formulations exhibited immediate drug release (> 80%) within 45 min. Furthermore, in vivo evaluation indicated effective taste masking and improved palatability.