Effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox

Abstract

Deferasirox is an oral iron chelator used for the treatment of chronic iron overload in blood transfusions. Deferasirox is a BCS Class II drug with low solubility and high permeability. In the formulation development stage for BCS Class II compounds, one of the main approaches is solubility enhancement to achieve better dissolution profiles, increased bioavailability and in some cases, dose reduction. The aim of the study was to investigate the effect of particle size and surfactant on the solubility, permeability and dissolution characteristics of deferasirox. Ball milling method was used to reduce the particle size of deferasirox. Pluronic F127 or sodium lauril sulfate (SLS) were selected as surfactants at different concentrations. The maximum increase in the solubility was obtained with 10% SLS at pH 1.2 (from 0.9 µg/mL to 333.7 µg/mL), and with 5% Pluronic F127 at pH 6.8 (from 46.8 µg/mL to 334.2 µg/mL). Dissolution studies revealed that time to dissolve 85% of deferasirox was decreased as a function of ball milling time and particle size. Permeability studies showed that, in 100 µM concentration, deferasirox permeability was significantly enhanced by all concentrations of SLS (p<0.05). With an increase in Pluronic F127 concentration, permeability of deferasirox was not altered (p>0.05). All these results clearly demonstrated that surfactant addition to the formulations was effective for solubility enhancement of deferasirox, and surfactant type in optimized concentrations was very crucial. Particle size reduction can be used as a promising approach to improve dissolution, and hence bioavailability of deferasirox.