Epitaxial 2D Nucleation of Metastable Polymorphs:  A 2D Version of Ostwald's Rule of Stages

Abstract

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.

Characterization and Selective Crystallization of Famotidine Polymorphs

“…The higher the nucleation barrier, the larger the metastable zone width of the polymorph is. 35 Therefore, the nucleation barrier of polymorph A of famotidine is larger than that of polymorph B.…”

Interlaced spiral growth and step splitting on a steroid crystal

“…We showed in previous work that crystals of the stable polymorph grown from ethanol solution have an extremely polar morphology (Fig. 1b) [25][26][27]. The (0 1 0) face is either absent or is rounded, whereas the opposite ð01 0Þ face is always flat [28].…”

“…The steroid crystal investigated in this study is the stable polymorph of 7aMNa (in full: (7a, 17a)-17-hydroxy-7-methyl-19-nor-17-pregn-5(10)-en-20-yn-3-one) [25][26][27]. This polymorph has a monoclinic P2 1 molecules in the unit cell arranged in an XYX 0 Y 0 succession along the b axis (Fig.…”

Heterogeneous 2D nucleation of the stable polymorphic form on the metastable form

“…If the free energies of the polymorphs have close values, concomitant polymorphism is expected and numerous examples are known [3]. A special case of concomitant polymorphism is found for 2D epitaxial nucleation of the metastable phase on the stable one [4,5] process, the nucleation of the stable form on the metastable one has been suggested before, but up to our knowledge, never observed in in situ experiments [6][7][8].…”

“…The steroid, to be abbreviated as 7aMNa, has two polymorphs: a monoclinic P2 1 structure [9] and a triclinic P1 structure [10]. The two polymorphs are monotropically related within the experimental temperature range and at room temperature the most stable form is the monoclinic one [4,5]. The starting material had the P2 1 structure and was supplied by N.V. Organon.…”