The prediction, morphology, and mechanical properties of the polymorphs of paracetamol

Beyer, Theresa, Day, Graeme M. and Price, Sarah L. (2001) The prediction, morphology, and mechanical properties of the polymorphs of paracetamol. Journal of the American Chemical Society, 123, (21), 5086-5094. (doi:10.1021/ja0102787).


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The analgesic drug paracetamol (acetaminophen) has two reported metastable polymorphs, one with better tabletting properties than the stable form, and another which remains uncharacterized. We have therefore performed a systematic crystal structure prediction search for minima in the lattice energy of crystalline paracetamol. The stable monoclinic form is found as the global lattice-energy minimum, but there are at least a dozen energetically feasible structures found, including the well-characterized metastable orthorhombic phase. Hence, we require additional criteria to reduce the number of hypothetical crystal structures that can be considered as potential polymorphs. For this purpose the elastic properties and vapor growth morphology of the known and predicted structures have been estimated using second-derivative analysis and the attachment-energy model. These inexpensive calculations give reasonable agreement with the available experimental data for the known polymorphs. Some of the hypothetical structures are predicted to have a low growth rate and platelike morphology, and so are unlikely to be observed. Another is only marginally mechanically stable. Thus, this first consideration of such properties in a crystal-structure prediction study appears to reduce the number of predicted polymorphs while leaving a few candidates for the uncharacterized form

Item Type: Article
Digital Object Identifier (DOI): doi:10.1021/ja0102787
ISSNs: 0002-7863 (print)
1520-5126 (electronic)
Subjects: Q Science > QD Chemistry
Divisions : Faculty of Natural and Environmental Sciences > Chemistry > Computational Systems Chemistry
Faculty of Natural and Environmental Sciences > Chemistry > Organic Chemistry: Synthesis, Catalysis and Flow
ePrint ID: 343466
Accepted Date and Publication Date:
Date Deposited: 19 Oct 2012 14:07
Last Modified: 31 Mar 2016 14:35

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