Crystallisation of Pyroglutamic Acid: Jumping Crystals and Polymorphic Transformation

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 industry^1-2. Our previous studies investigated the enantiotropic polymorphs of L-Pyroglutamic acid α’, α and β and their phase transformations sequence^3-4:

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.

References

[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.