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Effect of pH, Counter Ion, and Phosphate Concentration on the Glass Transition Temperature of Freeze-Dried Sugar-Phosphate Mixtures

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Abstract

Purpose. The aim of the present work is to study the interaction of phosphate salts with trehalose and sucrose in freeze-dried matrices, particularly the effect of the salts on the glass transition temperature (Tg) of the sugars.

Methods. Freeze-dried trehalose and sucrose systems containing different amounts of sodium or potassium phosphate were analyzed by differential scanning calorimetry to determine the Tg and by Fourier-transform infrared spectroscopy (FTIR) analysis to evaluate the strength of the interaction between sugars and phosphate ions.

Results. Sucrose-phosphate mixtures show an increase in Tg up to 40°C in a broad pH range (4-9) compared to that of pure sucrose. Sucrose-phosphate mixtures exhibit a higher Tg than pure sucrose while retaining higher water contents. Trehalose-phosphate mixtures (having a Tg of 135°C at a pH of 8.8) are a better option than pure trehalose for preservation of labile materials. The -OH stretching of the sugars in the presence of phosphates decreases with increase in pH, indicating an increase in the sugar-phosphate interaction.

Conclusions. Sugar-phosphate mixtures exhibit several interesting features that make them useful for lyophilization of labile molecules; Tg values much higher than those observed for the pure sugars can be obtained upon the addition of phosphate.

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Authors and Affiliations

  1. Chemical and Biological Engineering Department, University of Wisconsin, Madison, Wisconsin, 53706, USA

    Satoshi Ohtake, Sean P. Palecek & Juan J. de Pablo

  2. Departamento de Industrias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, (1428), Ciudad Autónoma de Buenos Aires, Argentina

    Carolina Schebor

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  1. Satoshi Ohtake
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  2. Carolina Schebor
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  3. Sean P. Palecek
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  4. Juan J. de Pablo
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Ohtake, S., Schebor, C., Palecek, S.P. et al. Effect of pH, Counter Ion, and Phosphate Concentration on the Glass Transition Temperature of Freeze-Dried Sugar-Phosphate Mixtures. Pharm Res 21, 1615–1621 (2004). https://doi.org/10.1023/B:PHAM.0000041456.19377.87

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  • DOI: https://doi.org/10.1023/B:PHAM.0000041456.19377.87

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