SOLID-STATE CHARACTERIZATION OF ZANOTERONE

Differential scanning calorimetry (DSC) data, in conjunction with Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffraction (XRPD), was used to discriminate various polymorphic forms of zanoterone. The solid-state degradation rate of form IV (hemihydrate A) was found to be greater than that of form III at 40 degrees C/25% RH and 40 degrees C/75% RH. At 40 degrees C/75% RH, the rate of degradation was 4-fold higher for form IV vs form III. Mixtures of forms III and IV were observed following desolvation of the acetonitrile solvate at 40 degrees C with humidity levels of 60 and 70% RH, while at 40 degrees C and 20-40% RH pure form III was formed. At 60 degrees C, a mixture of forms III and IV was observed at 70% RH but not at lower relative humidity. The concentration of each form of zanoterone in solution was measured as a function of time at room temperature in 3% sodium lauryl sulfate. Forms I, II, and V showed greater initial concentrations than form III, but the values decreased with time due to the precipitation of form VI (hemihydrate B). Therefore, concentrations measured for forms I, II, and V were not equilibrium solubilities for these forms. Forms IV and VI showed lower initial concentrations (than form III) which did not change significantly with time.