Effect of PH, Counter Ion, and Phosphate Concentration on the Glass Transition Temperature of Freeze-dried Sugar-phosphate Mixtures

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2004 Oct 23

PMID 15497687

Citations 14

Authors

Satoshi Ohtake

Carolina Schebor

Sean P Palecek

Juan J de Pablo

Affiliations

Soon will be listed here.

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.

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References

Duddu S, Dal Monte P . Effect of glass transition temperature on the stability of lyophilized formulations containing a chimeric therapeutic monoclonal antibody. Pharm Res. 1997; 14(5):591-5. DOI: 10.1023/a:1012144810067. View

Wolkers W, Oldenhof H, Alberda M, Hoekstra F . A Fourier transform infrared microspectroscopy study of sugar glasses: application to anhydrobiotic higher plant cells. Biochim Biophys Acta. 1998; 1379(1):83-96. DOI: 10.1016/s0304-4165(97)00085-8. View

Uritani M, Takai M, Yoshinaga K . Protective effect of disaccharides on restriction endonucleases during drying under vacuum. J Biochem. 1995; 117(4):774-9. DOI: 10.1093/oxfordjournals.jbchem.a124775. View

Mazzobre M, Del Pilar Buera M . Combined effects of trehalose and cations on the thermal resistance of beta-galactosidase in freeze-dried systems. Biochim Biophys Acta. 1999; 1473(2-3):337-44. DOI: 10.1016/s0304-4165(99)00207-x. View

Ohtake S, Schebor C, Palecek S, de Pablo J . Effect of sugar-phosphate mixtures on the stability of DPPC membranes in dehydrated systems. Cryobiology. 2004; 48(1):81-9. DOI: 10.1016/j.cryobiol.2004.01.001. View

Buitink J, van den Dries I, Hoekstra F, Alberda M, Hemminga M . High critical temperature above T(g) may contribute to the stability of biological systems. Biophys J. 2000; 79(2):1119-28. PMC: 1301007. DOI: 10.1016/S0006-3495(00)76365-X. View

Conrad P, Miller D, Cielenski P, de Pablo J . Stabilization and preservation of Lactobacillus acidophilus in saccharide matrices. Cryobiology. 2000; 41(1):17-24. DOI: 10.1006/cryo.2000.2260. View

TAYLOR L, Zografi G . Sugar-polymer hydrogen bond interactions in lyophilized amorphous mixtures. J Pharm Sci. 1999; 87(12):1615-21. DOI: 10.1021/js9800174. View

Koster K, Leopold A . Sugars and desiccation tolerance in seeds. Plant Physiol. 1988; 88(3):829-32. PMC: 1055669. DOI: 10.1104/pp.88.3.829. View

10.

Miller D, Anderson R, de Pablo J . Stabilization of lactate dehydrogenase following freeze thawing and vacuum-drying in the presence of trehalose and borate. Pharm Res. 1998; 15(8):1215-21. DOI: 10.1023/a:1011987707515. View

11.

MacFarlane D, Pringle J, Annat G . Reversible self-polymerizing high T(g) lyoprotectants. Cryobiology. 2002; 45(2):188-92. DOI: 10.1016/s0011-2240(02)00127-x. View

12.

Tzannis S, Prestrelski S . Moisture effects on protein-excipient interactions in spray-dried powders. Nature of destabilizing effects of sucrose. J Pharm Sci. 1999; 88(3):360-70. DOI: 10.1021/js9800127. View

13.

Crowe J, Carpenter J, Crowe L . The role of vitrification in anhydrobiosis. Annu Rev Physiol. 1998; 60:73-103. DOI: 10.1146/annurev.physiol.60.1.73. View

14.

Crowe L, Reid D, Crowe J . Is trehalose special for preserving dry biomaterials?. Biophys J. 1996; 71(4):2087-93. PMC: 1233675. DOI: 10.1016/S0006-3495(96)79407-9. View

15.

Randolph T . Phase separation of excipients during lyophilization: effects on protein stability. J Pharm Sci. 1997; 86(11):1198-203. DOI: 10.1021/js970135b. View

16.

Carpenter J, Hand S, Crowe L, Crowe J . Cryoprotection of phosphofructokinase with organic solutes: characterization of enhanced protection in the presence of divalent cations. Arch Biochem Biophys. 1986; 250(2):505-12. DOI: 10.1016/0003-9861(86)90755-1. View

17.

Miller D, de Pablo J, Corti H . Thermophysical properties of trehalose and its concentrated aqueous solutions. Pharm Res. 1997; 14(5):578-90. DOI: 10.1023/a:1012192725996. View

18.

Mazzobre M, Longinotti M, Corti H, Buera M . Effect of salts on the properties of aqueous sugar systems, in relation to biomaterial stabilization. 1. Water sorption behavior and ice crystallization/melting. Cryobiology. 2002; 43(3):199-210. DOI: 10.1006/cryo.2001.2345. View

19.

van den Berg L, Rose D . Effect of freezing on the pH and composition of sodium and potassium phosphate solutions; the reciprocal system KH2PO4-Na2-HPO4-H2O. Arch Biochem Biophys. 1959; 81(2):319-29. DOI: 10.1016/0003-9861(59)90209-7. View