Solubility Model to Guide Solvent Selection in Synthetic Process Development

Solvent
selection to obtain adequate yield and impurity rejection
is a critical activity in the development of crystallization processes
for synthetic chemicals. This activity requires the determination
of solubilities for a solute (moreover, a polymorph of a solute) in
a variety of solvents and solvent combinations. A model was developed
to facilitate the exploration solubility for single solvent systems.
This model is based on the dynamics of incorporation events at discrete
interfaces that are most applicable at temperatures far from the melt.
Parameters within the model were trained, hyper-parameters tuned,
and model performance cross-validated using a set of ∼500 solubility
measurements across a variety of solutes and solvents. Cross-validation
predictions appear unbiased and accurate, with errors approximated
by a log10-normal distribution described by a mean and
standard deviation of 0.011 and 0.197, respectively.