Mesoporous silica-based amorphous solid dispersions to enhance the oral bioavailability of Neratinib maleate

Abstract

Neratinib maleate (NM) used in the treatment of breast cancer, has a low and variable oral bioavailability due to its pH-dependent solubility and gut-wall metabolism-restricted permeability. Mesoporous silica based solid dispersion of NM (SD-NM-MSi) was designed to improve its solubility and dissolution rate. SYLOID XDP 3050 was selected as a mesoporous silica carrier based on its higher drug loading (15.7 %) and good flow properties. The extensive surface area of the Mesoporous silica offered a suitable site for drug adsorption. Thermal and diffractometry analysis indicated that NM was adsorbed in an amorphous form. In vitro dissolution studies revealed that the optimized SD-NM-MSi showed a higher rate and extent of drug dissolution compared to plain NM in pH 3.0, pH 4.5, and 6.8, respectively. Similarly, an oral pharmacokinetic study (10 mg/kg) resulted in significantly higher plasma exposure for SD-NM-MSi compared to plain NM, with a 73 % (P < 0.01) increase in the relative oral bioavailability of NM.