The extreme polar morphology that has been observed for crystals of the stable form of a steroid is explained by a molecular dynamics simulations approach. The habit modification is caused by surface-solvent interactions, which affect the growth rate of the polar faces differently. The same effect was observed for the metastable polymorphic form. Depending on the solvent, the nature of the difference is mainly caused by the hydrogen bond interactions or the electrostatic part of the interactions.

We present in-situ observations of the epitaxial nucleation of the metastable polymorph of a steroid on specific faces of the stable form in different solutions using optical microscopy. The polar morphology of the crystals allows for the determination of the specific face where the epitaxial nucleation takes place. The observations prove that there is a different barrier for 2D epitaxial nucleation of the metastable polymorph on the opposite polar faces. In-situ Raman measurements are used to confirm the structure of the epitaxially growing crystals. The metastable zone width and the role of the solvent in this process are discussed. The relatively large lifetime of the metastable polymorph in ethanol solutions is exploited to determine the solubility curves of the bulk phases of both polymorphs. The relation between the solubility of the two polymorphs in different solvents and the polymorphic transformation rate is discussed.

Using in situ polarization microscopy and in situ Raman spectroscopy, a polymorphic phase transition from the triclinic to the monoclinic crystal form of 7-R-methyl-∆5,10-norethindrone has been observed in acetone solutions at room temperature. The metastable triclinic form is nucleated epitaxially on the stable monoclinic form beyond a threshold supersaturation. The metastable phase transforms into the stable phase by a solidsolute-solid mechanism in acetone. The thermodynamics of ordinary and epitaxial nucleation are discussed.

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