This paper describes a method for the laboratory-scale crystallization of the orthorhombic polymorph (form II) of paracetamol (acetaminophen) from solution. Its structure has been determined by single-crystal X-ray crystallography at 298 K (to confirm the results of data published in 1974) and at 123 K (to improve the overall accuracy of the structure determination). Despite considerable effort by many investigators, the crystallization of form II from solution, using the method given in the 1974 structure report, has been elusive. The incentive for this effort is that form II, unlike commercial paracetamol (form I), undergoes plastic deformation and is suitable for direct compression. Consequently, the ability to produce form II in quantity has attracted much interest because of the potential commercial benefits to be gained by not using binders during the manufacture of tablets. However, until now, the only method that has been reported for the bulk preparation of form II has been to grow it as polycrystalline material from fused form I. This study also compares the solid-state properties of form II with those of form I, with particular emphasis on the crystallography (both X-ray and optical), crystal morphology, thermal behavior, and compaction properties.
Article:Nguyen, TTH, Hammond, RB, Roberts, KJ et al. (2 more authors) (2014) Precision measurement of the growth rate and mechanism of ibuprofen {001} and {011} as a function of crystallization environment. CrystEngComm, 16 (21). 4568 -4586. ISSN 1466-8033 https://doi.org/10.1039/c4ce00097h eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website.
TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. acetonitrile. The crystal growth rates of the {001} and {011} faces of spontaneously nucleated crystals are precisely measured in-situ using optical microscopy revealing that their respective growth rates increase with increasing supersaturation to different extents, depending on the solvent type, with concomitant impact on the crystal habit. The measured aspect ratios, as a function of supersaturation, are generally higher at the 15 mL than the 0.5 mL scale size.Analysis of the growth rates versus supersaturation is consistent with a 2-D surface nucleation (Birth and Spread) model for both faces and at both scale sizes. The growth rates of the {001} and {011} faces exhibit much less growth rate dispersion when compared to literature data for a stirred batch crystallizer.
2The data is rationalized by examining the surface chemistry of the growing faces revealing, e.g. that polar protic solvents inhibit the growth rate of faces containing available binding sites for hydrogen bonding formation, such as carboxylic acid groups.
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