Drug enabling strategies for oral delivery of a poorly soluble antimalarial: amorphous solid dispersions and self-emulsifying systems via hot-melt extrusion

This impairment is linked to disruption of Soluplus®-mediated micellisation by RH40, an effect that intensified with increasing RH40-to-Soluplus® ratio.<br><br>A solid SEDDS design integrating ASD principles was then developed. A two-step HME process, amorphisation followed by lipid incorporation, enabled manufacture of solid SEDDS with >40% DL. Within these systems, LUM reverted to a crystalline state, mitigating the risks associated with amorphous instability.

Ternary ASD-derived SEDDS exhibited distinctive pH-responsive dissolution: an initial burst release with precipitation in acidic medium, followed by pronounced re-solubilisation upon neutralisation. The transient formation of an amorphous intermediate during processing contributed to matrix homogenisation and enhanced pH-triggered solubilisation. Furthermore, this secondary solubilisation appeared to be linked to pH-triggered colloidal reorganisation.

The platform was successfully extended to ART–LUM co-loaded SEDDS pellets, which preserved pH-responsive release and delivered superior dissolution of both actives compared to single-loaded SEDDS and a marketed reference, demonstrating its translational potential.<br><br><i>Thesis is embargoed until 31 July 2031.</i><br>