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    An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression.

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    Authors
    Kaialy, Waseem
    Larhrib, Hassan
    Chikwanha, Brian
    Shojaee, Saeed
    Nokhodchi, Ali
    Issue Date
    2014-04-10
    
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    Abstract
    Paracetamol is a popular over-the-counter analgesic and a challenging model drug due to its poor technological and biopharmaceutical properties such as flowability, compressibility, compactibility and wettability. This work was aimed to alter the crystal habit of paracetamol from elongated to polyhedral-angular via particle engineering whilst maintaining the stable polymorphic form (form I: monoclinic form). The engineered paracetamol crystals obtained in the present investigation showed better technological and biopharmaceutical properties in comparison to the commercial paracetamol. Engineered paracetamol crystals were obtained using antisolvent crystallization technique in the presence of various concentrations (0.1, 0.5 and 1%, w/w) of additives, namely, polyvinyl alcohol (PVA), Avicel PH 102 (microcrystalline cellulose), Brij 58, methylcellulose (MC) and polyethylene glycol having different molecular weights (PEGs 1500, 6000 and 8000). Paracetamols crystallized in the presence of Avicel (or physically mixed with Avicel), Brij 58 and PEG 6000 demonstrated the best compactibility over a range of compaction pressures. Brij-crystallized paracetamol provided the fastest dissolution rate among all the paracetamol batches. Paracetamols crystallized in the presence of PVA or Avicel, or physically mixed with Avicel demonstrated a reduced degree of crystallinity in comparison to the other paracetamols. This study showed that the type, the grade and the concentration of additives could influence the physical stability such as flow, crystallinity and polymorphic transformation of paracetamol, the technological and biopharmaceutical properties of paracetamol. Stable polymorphic form of paracetamol with optimal tableting characteristics can be achieved through particle engineering.
    Citation
    An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression. 2014, 464 (1-2):53-64 Int J Pharm
    Journal
    International journal of pharmaceutics
    URI
    http://hdl.handle.net/2436/620513
    DOI
    10.1016/j.ijpharm.2014.01.026
    PubMed ID
    24480534
    Type
    Journal article
    Language
    en
    ISSN
    1873-3476
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ijpharm.2014.01.026
    Scopus Count
    Collections
    Faculty of Science and Engineering

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