Pseudopolymorphism (solvates)
Prior to this, the presence of solvates or false polymorphs,
sometimes (incorrectly and confusingly)
called pseudopolymorphs, should be identified, as
most polymorphs can be obtained by changing the
recrystallizing solvent. Typical solvents inducing
polymorphic change are water, methanol, ethanol,
acetone, chloroform, n-propanol, isopropanol
alcohol, w-butanol, n-pentanol, toluene and benzene.
Trace levels of solvent are usual in early batches of
new drug candidates (residues from the final crystallization).
These can become molecular additions to
the crystal and change habit. These hydrates (water)
and solvates (e.g. methanolate, ethanolate) have
been confused with true polymorphism and have led
to the term pseudopolymorphism.
The distinction between these false forms and true
polymorphs can be ascertained by observing the
melting behaviour of the compound dispersed in silicone
oil using hot-stage microscopy.
Pseudopolymorphs will evolve a gas (steam or
solvent vapour), causing the oil to bubble. True
Fig. 8.4 The relationship between in vitro and in vivo release from fluprednisolone implants.
polymorphs merely melt, forming a second globular
phase. The temperature at which the solvent volatilizes
will be close to the boiling point of the solvent.