Metastable Polymorph of Etoposide with Higher Dissolution Rate

Abstract

Etoposide, an anticancer drug, has low oral bioavailability because of low aqueous solubility, slow dissolution rate, and instability in acidic pH. Our objective was to enhance the aqueous solubility and dissolution rate of etoposide by polymorph formation. Preparation of various polymorphs of etoposide was attempted by crystallizing etoposide from organic solvents. Physicochemical properties of the crystals, namely, crystal habit, thermal behavior with hot-stage microscopy, thermal analysis by differential scanning calorimetry, IR spectrum, and solubility and dissolution rates, were examined. Based on the physicochemical characteristics, a metastable polymorph of etoposide was identified when it was crystallized from isopropanol. The metastable polymorph had an equilibrium solubility and intrinsic dissolution rate of 221 μg/ml and 16.3 μg/min/cm², respectively; 1.9 and 1.7 times that of etoposide powder at 25°C, respectively.