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Research Article Pharmaceutics, Drug Delivery and Pharmaceutical Technology| Volume 108, ISSUE 6, P2128-2135, June 01, 2019

Overcoming Poor Tabletability of Bulky Absorption Enhancers by Spray Drying Technology

  • Weiwei Fan
    Affiliations
    Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

    School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China
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  • Aohua Wang
    Affiliations
    Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

    School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China
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  • Yue Wu
    Affiliations
    Novo Nordisk Research Centre China, Department of Pharmacology and Histopathology, Discovery Biology China, Beijing 102206, China
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  • Jorrit J. Water
    Affiliations
    Global Research Technologies, Novo Nordisk A/S, Maalov 2760, Denmark
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  • Stephen T. Buckley
    Affiliations
    Global Research Technologies, Novo Nordisk A/S, Maalov 2760, Denmark
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  • Lars Hovgaard
    Affiliations
    Global Research Technologies, Novo Nordisk A/S, Maalov 2760, Denmark
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  • Mingshi Yang
    Correspondence
    Correspondence to: Mingshi Yang (Telephone: +45 35336141) and Yong Gan (Telephone: +86 20231975).
    Affiliations
    Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark

    Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, Shenyang, China
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  • Yong Gan
    Correspondence
    Correspondence to: Mingshi Yang (Telephone: +45 35336141) and Yong Gan (Telephone: +86 20231975).
    Affiliations
    Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

    School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China
    Search for articles by this author
Published:February 02, 2019DOI:https://doi.org/10.1016/j.xphs.2019.01.025

      Abstract

      Absorption enhancers are often a major component of solid oral peptide formulations as compared to the active pharmaceutical ingredient and excipients. This commonly results in poor tabletability that is hard to mitigate in direct compaction by addition of small amounts of excipients. To improve the tabletability of bulky absorption enhancers, the model absorption enhancers, sodium cholate and deoxycholic acid, were co–spray-dried with hydroxypropyl methylcellulose E5, where the percentage of absorption enhancers was not lower than 90% (w/w). The physicochemical properties of the resulting powders were assessed by laser diffraction, scanning electron microscopy, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry. The powders were compressed into tablets, and the tabletability was evaluated. Co–spray drying with 10% of hydroxypropyl methylcellulose significantly improved the tabletability of the both absorption enhancers. Moreover, it was demonstrated that small particle size and amorphous state rather than high moisture content contributed to the improved tabletability of the spray-dried powders. The study suggests that spray drying technology can be promising to overcome the poor tabletability of oral peptide formulation consisting of large amounts of absorption enhancers.

      Keywords

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