Preformulation study for the selection of a suitable polymer for the development of ellagic acid-based solid dispersion using hot-melt extrusion.

Ellagic acid is one of the most studied polyphenolic compounds due to its numerous promising therapeutic properties. However, this therapeutic potential remains difficult to exploit owing to its low solubility and low permeability, resulting in low oral bioavailability. In order to allow an effective therapeutic application of EA, it is therefore necessary to develop strategies that sufficiently enhance its solubility, dissolution rate and bioavailability. For this purpose, solid dispersions based on pre-selected polymers such as Eudragit® EPO, Soluplus® and Kollidon® VA 64, with 5% w/w ellagic acid loading were prepared by hot extrusion and characterized by X-ray diffraction, FTIR spectroscopy and in vitro dissolution tests in order to select the most suitable polymer for future investigations. The results showed that Eudragit® EPO was the most promising polymer for ellagic acid solid dispersions development because its extrudates allowed to obtain a solution supersaturated in ellagic acid that was stable for at least 90 min. Moreover, the resulting apparent solubility was 20 times higher than the actual solubility of ellagic acid. The extrudates also showed a high dissolution rate of ellagic acid (96.25% in 15 min), compared to the corresponding physical mixture (6.52% in 15 min) or the pure drug (1.56% in 15 min). Furthermore, increasing the loading rate of ellagic acid up to 12% in extrudates based on this polymer did not negatively influence its release profile through dissolution tests.

Physical formulation approaches for improving aqueous solubility and bioavailability of ellagic acid: A review.

Ellagic acid (EA) is a polyphenolic active compound with antimalarial and other promising therapeutic activities. However, its solubility and its permeability are both low (BCS IV). These properties greatly compromise its oral bioavailability and clinical utilizations. To overcome these limitations of the physicochemical parameters, several formulation approaches, including particle size reduction, amorphization and lipid-based formulations, have been used. Although these strategies have not yet led to a clinical application, some of them have resulted in significant improvements in the solubility and bioavailability of EA. This critical review reports and analyses the different formulation approaches used by scientists to improve both the biopharmaceutical properties and the clinical use of EA.