Issue 13, 2019

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

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.

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

Supplementary files

Article information

Article type
Paper
Submitted
25 Okt. 2018
Accepted
16 Febr. 2019
First published
15 Marts 2019
This article is Open Access
Creative Commons BY license

CrystEngComm, 2019,21, 2234-2243

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

M. J. Vesga, D. McKechnie, P. A. Mulheran, K. Johnston and J. Sefcik, CrystEngComm, 2019, 21, 2234 DOI: 10.1039/C8CE01829D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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