Thermodynamic vs. kinetic basis for polymorph selection 
Hodnett, Benjamin K.; Verma, Vivek



Ratios of equilibrium solubilities rarely exceed twofold for polymorph pairs. A model
has been developed based on two intrinsic properties of polymorph pairs, namely the ratio of equilibrium solubilities of the individual pairs (C*me/C*st) and the ratio of interfacial energies (st/me) and one applied experimental condition,
namely the supersaturation identifies which one of a pair of polymorphs nucleates first.
A domain diagram has been developed, which identifies the point where the critical free energy of nucleation for the polymorph pair are identical. Essentially, for a system supersaturated with respect to both polymorphs, the model identifies that low supersaturation with respect to the stable polymorph (Sst) leads to an extremely small supersaturation with respect to the metastable polymorph (Sme), radically driving up the critical free energy with respect to the metastable polymorph. Generally, high supersaturations sometimes much higher than the upper
limit of the metastable zone, are required to kinetically favour the metastable polymorph

Keyword(s):

classical nucleation theory; polymorphs; interfacial energy; solubility; supersaturation; metastable zone width 
Publication Date:

2019 
Type:

Journal article 
PeerReviewed:

Yes 
Language(s):

English 
Institution:

University of Limerick 
Funder(s):

Science Foundation Ireland 
Citation(s):

12RC2275 Processes 7, 272 12/RC/2275 
Publisher(s):

MDPI 
First Indexed:
20190519 06:25:20 Last Updated:
20190629 06:47:47 