198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

180 M.R. Caira
described as general. However, since systematic study of the factors which might
be involved in effecting or affecting polymorphic transformation in these cases
could in principle find wider application, brief mention of such examples is
made here. The effect of explosion on polymorphs of chitin and chitosan has
recently been studied [93]. Explosion of a-chitin resulted in no change, but
explosion of hydrated chitosan of low crystallinity yielded a product with
increased crystallinity as well as a small amount of the anhydrous phase. The
effect of an electric field on polymorphic transformation in certain classes of
compounds may be a phenomenon warranting systematic investigation. Strong
temperature-dependence of the bÆapolymorphic transition of isotactic polypropylene
(containing additives) has been observed when the system is exposed
to an electric field [94]. The effects of neutron-irradiation on the kinetics of
polymorphic phase transitions for several inorganic compounds have been
reported [95], but similar studies using organic compounds as substrates are
lacking. It has, however, been demonstrated that ionizing radiation can induce a
polymorphic transformation in an organic compound.A polycrystalline sample
of the b-polymorph of a diacetylene nitroxide has been reported to undergo
transition to the a-polymorph on irradiation with CuKa or 60 Co sources [96].
X-ray powder diffraction was used to monitor this phase tranformation.
Finally, the role of serendipity in producing polymorphs may be mentioned.
Two recent cases involved unsuccessful attempts to produce molecular complexes
by reaction of two components in solution, resulting instead in the precipitation
of crystals of one component in a desirable polymorphic form.
Attempts to grow crystals of methotrexate by various techniques failed [97].
However, tetragonal crystals of the compound were obtained from a solution
containing methotrexate and thymidine, prepared for the purpose of obtaining
a co-crystal of these components. Similarly, attempted complexation between
5-sulphamethoxydiazine and p-aminosalicylic acid failed, the solution of these
species in a 1:1 molar ratio producing instead large crystals of Form II of the
sulphonamide [98]. Interestingly, this polymorph of the drug is the biologically
most active form and is usually crystallized from ethanol followed by rapid
cooling of the solution to –12 °C. This yields small particles with little or no geometrical
form [99]. A possible explanation for the crystallization of Form II
during attempts to produce the complex has been discussed [98].
3.2
Review of Investigative Methods
Having outlined the methods of preparation of polymorphs and pseudopolymorphs,
this report now focuses on the methodology used to study these forms.
The discussion commences with a survey of some well established and still
widely used techniques, each of which is illustrated by one or more applications.
This is followed by a survey of newer methodology which is being used to
probe organic crystal polymorphism.
A wide spectrum of analytical techniques may be used to characterize polymorphs
and pseudopolymorphs in terms of their structure, spectral energies,
thermodynamic stabilities, kinetics of transformation and solubility behaviour.