Moldovan, AA orcid.org/0000-0003-2776-3879, Rosbottom, I orcid.org/0000-0001-6342-3973, Ramachandran, V et al. (3 more authors) (2017) Crystallographic Structure, Intermolecular Packing Energetics, Crystal Morphology and Surface Chemistry of Salmeterol Xinafoate (Form I). Journal of Pharmaceutical Sciences, 106 (3). pp. 882-891. ISSN 0022-3549
Abstract
Single crystals of salmeterol xinafoate (form I), prepared from slow cooled supersaturated propan-2-ol solutions, crystallise in a triclinic P‾1 symmetry with two closely related independent salt pairs within the asymmetric unit, with an approximately double unit cell volume compared to the previously published crystal structure(1). Synthonic analysis of the bulk intermolecular packing confirms the similarity in packing energetics between the two salt pairs. The strongest synthons, as expected, are dominated by coulombic interactions. Morphological prediction reveals a plate-like morphology, dominated by the {001}, {010} and {100} surfaces, consistent with experimentally grown crystals. Though surface chemistry of the slow growing {001} face comprises of large sterically hindering phenyl groups, weaker coulombic interactions still prevail from the alcohol group present on the phenyl and hydroxymethyl groups. The surface chemistry of the faster growing {010} and {100} faces are dominated by the significantly stronger cation/anion interactions occurring between the carboxylate and protonated secondary ammonium ion groups. The importance of understanding the cohesive/adhesive nature of the crystal surfaces of an API, with respect to their interaction with other API crystals and excipients and how that may impact formulation design is highlighted.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Elsevier. This is an author produced version of a paper published in Journal of Pharmaceutical Sciences. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Molecular modelling; X-ray diffraction; crystal structure; formulation design; lattice energy; morphology; polymorphism; pulmonary drug delivery; salmeterol xinafoate; surface chemistry; synthonic engineering |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Dec 2016 16:17 |
Last Modified: | 12 Dec 2024 15:35 |
Published Version: | https://doi.org/10.1016/j.xphs.2016.11.016 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.xphs.2016.11.016 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:108859 |