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    Cocrystal habit engineering to improve drug dissolution and alter derived powder properties

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    Publication date
    2016-05
    Author
    Serrano, D.R.
    O'Connell, P.
    Paluch, Krzysztof J.
    Walsh, D.
    Healy, A.M.
    Keyword
    Cocrystal habit; Dissolution; Flowability; Tabletability; Wettability
    Rights
    © 2015 Royal Pharmaceutical Society. Reproduced in accordance with the publisher's self-archiving policy.
    Peer-Reviewed
    Yes
    
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    Abstract
    Objectives: Cocrystallization of sulfadimidine (SDM) with suitable coformers, such as 4-aminosalicylic acid (4-ASA), combined with changes in the crystal habit can favourably alter its physicochemical properties. The aim of this work was to engineer SDM:4-ASA cocrystals with different habits in order to investigate the effect on dissolution, and the derived powder properties of flow and compaction. Methods: Cocrystals were prepared in a 1:1 molar ratio by solvent evaporation using ethanol (habit I) or acetone (habit II), solvent evaporation followed by grinding (habit III) and spray-drying (habit IV). Key findings: Powder X-ray diffraction showed Bragg peak position was the same in all the solid products. The peak intensity varied, indicating different preferred crystal orientation confirmed by SEM micrographs: large prismatic crystals (habit I), large plate-like crystals (habit II), small cube-like crystals (habit III) and microspheres (habit IV). The habit III exhibited the fasted dissolution rate; however, it underwent a polymorphic transition during dissolution. Habits I and IV exhibited the highest Carr’s compressibility index, indicating poor flowability. However, habits II and III demonstrated improved flow. Spray drying resulted in cocrystals with improved compaction properties. Conclusions: Even for cocrystals with poor pharmaceutical characteristics, a habit can be engineered to alter the dissolution, flowability and compaction behavior.
    URI
    http://hdl.handle.net/10454/13683
    Version
    Accepted Manuscript
    Citation
    Serrano DR, O’Connell P, Paluch KJ et al (2016) Cocrystal habit engineering to improve drug dissolution and alter derived powder properties. Journal of Pharmacy and Pharmacology. 68(5): 665-677.
    Link to publisher’s version
    http://dx.doi.org/10.1111/jphp.12476
    Type
    Article
    Collections
    Life Sciences Publications

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