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| The objective of this work is to accurately measure the solid-state transformation temperature (Ttr) of two crystalline forms (form Ⅰ and form Ⅱ) of gestodene by three distinct methods. The polymorphic transformation among two polymorphs (form Ⅰ to form Ⅱ) was observed by differential scanning calorimetry (DSC) and variable temperature X-ray powder diffraction (VT-XRPD) measurements. Therefore, Ttr was evaluated as the onset transformation temperature by DSC at seven different heating rates ranging from 2 to 20 K min-1. In the solubility data method, Ttr is calculated as the temperature at which solubilities of the two forms are equal to each other. The solubility data of both polymorphs were measured gravimetrically in ethanol in the temperature range from 268.15 to 333.15 K under the atmospheric pressure of 0.10 MPa. The experimental solubility data were used to calculate the solid-solid transformation temperature based on the modified Apelblat and van't Hoff equation. In the last method, Ttr is determined directly by experimental studies of the temperature ranges of the stability of each polymorph. The mixture of both forms was agitated in a saturated solution at the programming temperature. X-ray powder diffractometer (XRPD) was used to determine the solid-state form of the residual crystals in suspension at equilibrium. The solid-solid transformation temperature of gestodene, determined with the DSC method, solubility data method and isothermal method, were found to be 313.44 K, 296.90 K (Apelblat equation), 298.11 K (van't Hoff equation) and 293.65 ± 0.5 K, respectively. As it can be observed, the mechanisms of the polymorphic transformation determined by different methods are different. Therefore, the calculated transformation temperature exhibits small difference by distinct methods. |
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| Keywords:Gestodene; Solid-state transformation temperature; Differential scanning calorimetry; X-ray powder diffraction; Solubility data |
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