Metastable polymorph of etoposide with higher dissolution rate

Etoposide, an anticancer drug, has low oral bioavailability because of low aqueous solubility, slow dissolution rate, and instability in acidic pH. Ou r objective was to enhance the aqueous solubility and dissolution rate of e toposide by polymorph formation. Preparation of various polymorphs of etopo side was attempted by crystallizing etoposide from organic solvents. Physic ochemical proper-ties of the crystals, namely, crystal habit, thermal behav ior with hot-stage microscopy, thermal analysis by differential scanning ca lorimetry, IR spectrum, and solubility and dissolution rates, were examined Based on the physicochemical characteristics, a metastable polymorph of et oposide was identified when it was crystallized from isopropanol. The metas table polymorph had an equilibrium solubility and intrinsic dissolution rat e of 221 mu g/ml and 16.3 mu g/min/cm(2), respectively; 1.9 and 1.7 times t hat of etoposide powder at 25 degrees C, respectively.