Conundrum of γ glycine nucleation revisited: to stir or not to stir?

Research output: Contribution to journalArticle

3 Citations (Scopus)
15 Downloads (Pure)

Abstract

Glycine polymorphism presents a conundrum: while the metastable α form of glycine typically crystallises in bulk cooling crystallisation from aqueous solution, both the highly unstable β and stable γ forms can be selectively crystallised in small scale cooling or evaporative experiments, without any additives, cosolvents or external fields. Small scale experiments in microwells or droplets differ from bulk crystallisation in some key aspects: absence of agitation, presence of large (and often very particular) surface areas per crystallisation volume, and ability to reach very high supersaturations. In this work we investigated effects of agitation on polymorphic outcomes in glycine crystallisation from aqueous solutions across a wide range of supersaturations at mL scale under quiescent conditions with and without a PTFE-coated magnetic stirrer (without any stirring) as well as under stirred conditions (with agitation supplied by the stirrer). In the absence of stirring, γ was predominant at higher glycine concentrations, which indicates that γ is more likely to nucleate than α in highly supersaturated aqueous solutions under quiescent conditions. Intriguingly, we found that under stirred conditions α was predominant at all concentrations and temperatures investigated. The effect of stirring on the preference for α glycine polymorphism cannot be fully explained by secondary nucleation alone. Instead, primary nucleation of glycine (at least of metastable forms) is strongly enhanced by stirring, in agreement with previous observations of shear effect on primary nucleation of glycine, and it is likely that similar effects play a role in other polymorphic systems of pharmaceutical interest.
Original languageEnglish
Pages (from-to)2234-2243
Number of pages10
JournalCrystEngComm
Issue number13
Early online date15 Mar 2019
DOIs
Publication statusPublished - 7 Apr 2019

Keywords

  • glycine polymorphism
  • crystallisation
  • stirred conditions

Fingerprint Dive into the research topics of 'Conundrum of γ glycine nucleation revisited: to stir or not to stir?'. Together they form a unique fingerprint.

  • Projects

    Cite this