(713f) Crystallisation of Pyroglutamic Acid: Jumping Crystals and Polymorphic Transformation

Coppens, M. O., University College London

L-pyroglutamic acid, an active
pharmaceutical material, has attracted intensive research interest both in
academic and industrial communities due to its importance in pharmaceutical and
food industry1-2. Our previous studies investigated the enantiotropic
polymorphs of L-Pyroglutamic acid α’, α and βand
their phase transformations sequence3-4:

The structural changes at the
transitions were studied by Raman spectroscopy and variable temperature powder
x-ray diffraction, and compared with single crystal structure determination. Differences
in Raman spectra were attributed to differences in intermolecular N-H···O
interactions in the three polymorphs. L-pyroglutamic acid racemized
spontaneously when heated above its melting temperature, ∼162 °C. This had a major effect on the
subsequent composition-dependent crystallization kinetics. Thus,
crystallization of L-pyroglutamic acid from undercooled melt was particularly
slow and required long-range counter-diffusion of L-pyroglutamic acid molecules
in the viscous, hydrogen-bonded melt.

In this study, a novel approach to
monitor the α↔β phase transformation was achieved using in
house Wide Angle X-ray Scattering (WAXS) with a linkam stage. By optical
microscopy, crystals frequently jumped around the microscope slide on passing
through the α/β transition; this is attributed to discontinuous
changes in the unit cell dimensions leading to a spring effect in the crystals. This thermosalient feature of the α→β
transformation was also confirmed by high speed camera and sequential weight
losses during repeated thermogravimetric cycling.


[1] Tan
S.W., et al., J Org Chem., 2015, 80 (5), 2661-2675.

[2] Heaton,
A.L., et al., US Patent US9066953, 2015.

[3] Wu, H., et al., Cryst. Growth Des., 2010,
10, 3141-3148.

[4] Wu, H and West, A.R., Cryst. Growth Des.,
2011, 11, 3366-3374.