Effect of pH, counter ion, and phosphate concentration on the glass transition temperature of freeze-dried sugar-phosphate mixtures

Pharm Res. 2004 Sep;21(9):1615-21. doi: 10.1023/b:pham.0000041456.19377.87.

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 degrees 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 degrees 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calorimetry, Differential Scanning
  • Freeze Drying
  • Hydrogen-Ion Concentration
  • Phosphates / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Sucrose / chemistry*
  • Temperature
  • Thermodynamics
  • Trehalose / chemistry*
  • Water / chemistry

Substances

  • Phosphates
  • Water
  • Sucrose
  • Trehalose