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The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides

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ABSTRACT

Purpose

To study how water plasticization affects the molecular mobility and crystallization tendency of freeze-dried trehalose, sucrose, melibiose and cellobiose.

Methods

Freeze-dried disaccharides were subjected to different relative humidity atmospheres and their physical stabilities were evaluated. Lyophilizate water sorption tendencies and glass transition temperatures were modeled using Brunauer-Emmett-Teller (BET) and Gordon-Taylor (GT) equations, respectively. Sucrose and cellobiose crystallization tendencies were compared by using the concept of reduced crystallization temperature (RCT), and the molecular mobilities of trehalose and melibiose were compared by measuring their T1H relaxation time constants.

Results

Based on the BET and GT models, water sorption tendency and the resulting plasticizing effect were different in sucrose when compared to the other disaccharides. Trehalose and melibiose exhibited generally slower crystallization rates when compared to sucrose and cellobiose. Amorphous melibiose was shown to be particularly stable within the studied water content range, which may have partly been caused by its relatively slow molecular mobility.

Conclusions

Slow amorphous-to-crystalline transition rate is known to be important for lyoprotecting excipients when formulating a robust drug product. The physical stabilities of amorphous trehalose and melibiose even with relatively high water contents might make their use advantageous in this respect compared to sucrose and cellobiose.

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ACKNOWLEDGMENTS & DISCLOSURES

The authors wish to acknowledge The Electron Microscopy Unit of the Institute of Biotechnology, University of Helsinki for providing laboratory facilities.

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Authors and Affiliations

  1. Industrial Pharmacy, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00014, Helsinki, Finland

    Ville Petteri Heljo, Antti Nordberg & Anne Mari Juppo

  2. Dept. of Physics & Astronomy, Faculty of Mathematics & Natural Sciences, University of Turku, Turku, Finland

    Mikko Tenho & Jarno Salonen

  3. Laboratory of Polymer Chemistry, Department of Chemistry Faculty of Science, University of Helsinki, Helsinki, Finland

    Tommi Virtanen & Sirkka Liisa Maunu

  4. Department of Food and Environmental Sciences Faculty of Agriculture and Forestry, University of Helsinki, Helsinki, Finland

    Kirsi Jouppila

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  1. Ville Petteri Heljo
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  2. Antti Nordberg
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Correspondence to Ville Petteri Heljo.

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Heljo, V.P., Nordberg, A., Tenho, M. et al. The Effect of Water Plasticization on the Molecular Mobility and Crystallization Tendency of Amorphous Disaccharides. Pharm Res 29, 2684–2697 (2012). https://doi.org/10.1007/s11095-011-0658-4

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  • DOI: https://doi.org/10.1007/s11095-011-0658-4

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