Deferasirox solid dispersions obtained by hot melt extrusion for increased solubility

The main objective of this research was to obtain solid dispersions of Deferasirox (DFX) by hot melt extrusion (HME), in order to promote improvementin the solubility of DFX as well as its dissolution rate.The polymer Soluplus® (SLP) was selected for the study, based on its ability to prevent the recrystallization of the active pharmaceutical ingredient (API) and mainly by the low glass transition temperature, which allows the API to be submitted to lower process temperatures, avoiding degradation. The proportions 90:10, 75:25 and 60:40 (polymer: active) were subjected to the HME process, conducted in a twinscrew extruder. The extruded material was characterized by thermal, physical-chemical, instrumental and optical analysis. The proportion 75:25 (DFXHME 75:25) obtained the best results, both in process and in the analytical stages. Therefore, dissolution tests and quantitative assessment of the solubility between DFX andDFXHME 75:25 were performed, indicating improvement of solubility in potassium phosphate buffer (PPB) pH 6.8. In the dissolution tests, the release percentage of DFXHME 75:25 reached approximately 95% (appr. 23.6 mg) in 10 minutes, while pure DFX was only 43.2% (appr. 10.8 mg). Already in the test for quantitative assessment of solubility, the difference between DFXHME 75:25 and pure DFX was 2.047 mg/mL, representing approximately98% increase in API solubility when extruded. Additionally, this proportion was evaluated by X-Ray diffractometry after 9 months of stability at room temperature and 6 months under accelerated conditions, obtaining positive results regarding the amorphization of the drug. Thus, the HMEprocess with SLP proved to be a viable and efficient alternative to provide increased solubility and dissolution rate of DFX by obtaining a stable amorphous solid dispersion.