Improvement water-solubility of ellagic acid for use as an antimalarial drug through oral administration

Ellagic acid (EA) is a polyphenolic compound, classed as a BCS IV drug, having anti-plasmodial activity on plasmodium-infected cell cultures. However, this class of molecules has a low oral bioavailability. The aim of our study is to increase the aqueous solubility and therefore the bioavailability of EA to allow its use orally as an antimalarial. To achieve this goal, solid dispersions of EA were made using the hot melt extrusion process.

For this purpose, a Scamex® twin-screw corotative extruder was used for the production of extrudates from mixtures of EA powders (5% w/w) and polymers (95% w/w). Three polymers were used as Eudragit® EPO, Kollidon VA® 64 and Soluplus®. The release profile of the EA from the extrudates was evaluated in vitro by dissolution tests under non sink conditions in acidic medium (0.1N HCl) and close to neutrality (pH 6.8 phosphate buffer).

Eudragit® EPO-based extrudates showed the best release profile of AE with a 94% release rate after 15 min while Kollidon VA® 64 and Soluplus® extrudates showed a dissolution of AE of 38.5% and 30.66%, respectively. The apparent solubility resulting from these release rates corresponded to a respective increase of 62, 25 and 20 times compared to the actual solubility of EA. Moreover, the supersaturated solutions of Eudragit® EPO and Soluplus® were stable for at least 1h30 min. In conclusion, the solid dispersion made of Eudragit® EPO and EA seems appropriated to enhance the oral bioavailability of the drug. More on this