Freeze dried solid dispersion of exemestane: A way to negate an aqueous solubility and oral bioavailability problems

This study was envisaged to demonstrate the potential of exemestane loaded phospholipid/sodium deoxycholate solid dispersions (EXE-PL/SDC-SDs) on the solubility and oral bioavailability of EXE. Initial studies were performed to screen the best suitable phospholipid among lysophosphatidylcholine, Phospholipon (R) P80H and Lipoid (R) E80S for solid dispersion preparation. Further studies were carried out to optimize the molar concentration of phospholipid and sodium deoxycholate (SDC) for EXE-PL/SDC-SDs preparation. Optimized EXEPL/SDC-SDs was prepared using Lipoid (R) E80S and SDC in 1: 4 M concentration, respectively and lyophilized using 10% w/w 2-hydroxypropyl-beta-cyclodextrin (2-HPCD). The physical state of EXE in lyophilized formulation was confirmed by DSC and PXRD. Lyophilized formulation exhibits a significant increase in solubility and dissolution rate as compared to free drug EXE. Apparent permeability study was performed on Caco-2 cell line for 2 h. The lyophilized EXE-PL/SDC-SDs exhibits 4.6-fold increase in absorptive transport as compared to EXE. Pharmacokinetic study in fasted female Sprague-Dawley rats revealed a 2.3-fold increase in AUC(0-72h). Thus, the results suggest that PL/SDC-SDs is a promising carrier for EXE delivery.