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Polymorphism of chlorpropamide on liquid-assisted mechanical treatment: choice of liquid and type of mechanical treatment matter

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Abstract

Different types of mechanical treatment (tableting, grinding, milling, etc.) are important technological operations in the pharmaceutical industry. Solid materials are not merely comminuted during such treatment, but can undergo polymorphic transitions and amorphisation. A liquid is often added to the solid sample on purpose, e.g. in order to facilitate comminution. In many cases, liquid is present inadvertently, either as a result of trace solvent following up-stream operations, or sorbed from the atmosphere. This work explores the liquid-assisted mechanical treatment of two metastable forms of a model pharmaceutical compound chlorpropamide (CPA), namely the β- and ε-forms. We investigate the stability of these polymorphs to mechanical treatment in the presence of a series of fluids that have affinity for different fragments of the CPA molecule. In addition to variation in fluids, the effect of different mechanical treatment is explored, employing model shear and restricted impact devices, alongside grinding in a mortar. CPA offers a clear example of the drastically different results of shear and impact on mechanochemical polymorphism, on the importance of the careful selection of solvent for liquid-assisted treatment, and on the possible role of even trace quantities of solvent. Further, this work demonstrates the importance of the starting polymorph in determining the outcome of a mechanochemical process. All of these factors can have notable consequence on the outcome of technological operations that include mechanical treatment.

Graphical abstract: Polymorphism of chlorpropamide on liquid-assisted mechanical treatment: choice of liquid and type of mechanical treatment matter

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Publication details

The article was received on 24 Dec 2017, accepted on 10 Feb 2018 and first published on 12 Feb 2018


Article type: Paper
DOI: 10.1039/C7CE02221B
Citation: CrystEngComm, 2018, Advance Article
  • Open access: Creative Commons BY license
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    Polymorphism of chlorpropamide on liquid-assisted mechanical treatment: choice of liquid and type of mechanical treatment matter

    N. Bouvart, R. Palix, S. G. Arkhipov, I. A. Tumanov, A. A. L. Michalchuk and E. V. Boldyreva, CrystEngComm, 2018, Advance Article , DOI: 10.1039/C7CE02221B

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