Solid dispersion formation by hot melt extrusion (HME) is a widely used formulation strategy to improve the
solubility and bioavailability of poorly water-soluble drugs. Despite this, they are limited by various factors such
as drug-excipient miscibility, poor stability, limited drug loading and extrudability of physical drug-excipient
mixtures. In this work, polyethylene glycol 8000 (PEG 8000) was used as a plasticizer for the manufacture of
ellagic acid solid dispersions (EASD) with high drug loading. Indeed, ellagic acid (EA) is a polyphenolic active
compound with antimalarial and other promising therapeutic activities. However, its low solubility and low
permeability limit its therapeutic use. Solid dispersions formation may overcome this challenge, but its high
melting point negatively influences the extrudability of its binary physical mixtures with a high drug loading rate,
hence the need to use a plasticizer. Thus, five formulations consisting of EA, Eudragit® EPO and PEG 8000 in the
ratio of 15:75:10 (F1), 20:70:10 (F2), 25:65:10 (F3), 15:80:5 (F4) and 20:85:5 (F5) % w/w, respectively, have
been extruded, four of which were successful. The extrudates were evaluated by X-ray powder diffraction, FTIR
spectroscopy and in vitro dissolution tests. Based on the results of these tests, the F5 formulation was identified as
the most promising. Indeed, after 15 min of dissolution test, the dissolution rate of ellagic acid from the
formulations was 62.67±3.10%, 58.74±7.23 %, 88.75±3.02% and 83.47±4.40% respectively for formulation F1,
F2, F4 and F5. Moreover, the results of the FTIR spectroscopy analyses showed stronger interactions between the
different constituents in the F4 and F5 formulations compared to the F1 and F2 formulations. Extruded materials
of the F5 formulation, characterized by solid state nuclear magnetic resonance (ssNMR) spectroscopy and
subjected to stability studies, showed good physical stability for twelve months under real-time stability study
conditions and for six months under accelerated conditions.

Ellagic acid, PEG 8000, ternary solid dispersions, hot melt extrusion, plasticizer, dissolution