Crystallization from the melt can
allow the achievement of high
driving force for crystallization accompanied by relatively slow growth,
nucleation, and transformation rates, features that favor its use
as an efficient polymorph screening method. Surprisingly, even though
melt crystallization has a long history, it has been employed less
often in the search for new polymorphs than solution crystallization.
Applications of melt crystallization to 21 highly polymorphic, well-characterized
compounds with at least five ambient polymorphs revealed that melt
crystallization afforded more than half of the known polymorphs and
in many cases revealed new polymorphs not detected by other screening
methods. A statistical analysis revealed that polymorphs grown from
the melt have a greater propensity for high Z′
values, which are not easily accessible by other crystallization protocols
and are often not detectable by crystal structure prediction methods.
Melt crystallization within nanopores (8–100 nm) performed
for 19 of the 21 compounds mostly resulted in polymorphs that dominated
crystallization from the bulk melt at similar temperatures. The total
number of polymorphs observed in nanopores was less than that observed
during crystallization from the bulk melt, however, and melt crystallization
under confinement revealed new polymorphs not detected by other crystallization
methods.