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

SATOSHI OHTAKE; CAROLINA SCHEBOR; SEAN P. PALECEK; JUAN J. DE PABLO

PHARMACEUTICAL RESEARCH

Springer

Año: 2004 vol. 21 p. 1615 - 1621

0724-8741

Purpose. The aim of the present work is to study the interaction ofphosphate 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 differentamounts of sodium or potassium phosphate were analyzed bydifferential scanning calorimetry to determine the Tg and by Fouriertransforminfrared spectroscopy (FTIR) analysis to evaluate thestrength of the interaction between sugars and phosphate ions.Results. Sucrose-phosphate mixtures show an increase in Tg up to40°C in a broad pH range (4–9) compared to that of pure sucrose.Sucrose-phosphate mixtures exhibit a higher Tg than pure sucrosewhile retaining higher water contents. Trehalose-phosphate mixtures(having a Tg of 135°C at a pH of 8.8) are a better option than puretrehalose for preservation of labile materials. The –OH stretching ofthe sugars in the presence of phosphates decreases with increase inpH, indicating an increase in the sugar-phosphate interaction.Conclusions. Sugar-phosphate mixtures exhibit several interestingfeatures that make them useful for lyophilization of labile molecules;Tg values much higher than those observed for the pure sugars can beobtained upon the addition of phosphate.