Batch and containerless crystallisation of L-glutamic acid in the presence and absence of amino acid additives

• Main Author: Rusin, Michal
• Other Authors: Ristic, Rile
• Published: University of Sheffield 2013
• Subjects: 572
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577446

Despite significant advances in recent years, our fundamental understanding and the ability to predict and control the polymorphic outcome of the crystallisation process remains limited. The aim of this work is to investigate how manipulation of the process conditions and application of new experimental strategies may provide new modes of polymorph selection during crystallisation from solution. In the first part of this thesis, batch crystallisation of pure and glycine-doped L-glutamic acid was investigated using single-photon laser light scattering and synchrotron wide angle X-ray scattering (WAXS) techniques. Surprisingly, in the presence of the additive, a marked increase in the amount of homogeneously nucleated β was observed, ultimately leading to a significant enhancement in the polymorphic transformation rate. Thus, for the first time, it was demonstrated that the crystallisation rates of one amino acid can be promoted using another amino acid as a doping material. The second part of this work focuses on the containerless crystallisation of L-glutamic acid from a droplet in an acoustic levitator. Using in-situ WAXS and Raman spectroscopy measurements, it was found that, contrary to the Ostwald's rule of stages, the more stable β is the first and only polymorph that forms. The metastable a did not nucleate even in the presence of the additives that have previously been reported to stabilise the metastable polymorph. It was postulated that the previously unreported selective crystallisation is due to a lower nucleation barrier for β at the surface of a droplet when compared to the centrosymmetric bulk. The entirely new effects presented in this work demonstrate how changing the crystallisation conditions may perturb the initial series of nucleation events and ultimately have a significant effect on the subsequent polymorphic transformation and thus on the crystallisation process as a whole. Furthermore, these original findings open new avenues of research and raise many fundamental questions on how nature finds intriguing ways to help crystallisation of the more stable polymorphic form. From the industrial standpoint, the insights derived from this study may contribute to the design of new nucleation and transformation modulators.