Effect of Initial Buffer Composition on pH Changes During Far-From-Equilibrium Freezing of Sodium Phosphate Buffer Solutions
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Purpose. This study aims to assess the pH changes induced by salt precipitation during far-from-equilibrium freezing of sodium phosphate buffers as a function of buffer composition, under experimental conditions relevant to pharmaceutical applications—sample volumes larger than a few microliters, experiencing large degrees of undercooling and supersaturation.
Methods. Buffer solutions were prepared by dissolving the monosodium and disodium phosphate salts in the appropriate ratios to obtain initial buffer concentrations in the range of 8-100 mM and pH values between 5.7 and 7.4 at 25°C. Temperature and pH were monitored in situ during cooling to −10°C (at a rate of 0.3 to 0.5°C/min) and for 10-20 min after the sample reached the final temperature. Salt crystallization was confirmed by ion analysis and x-ray powder diffraction.
Results. Precipitation of Na2HPO4 · 12H2O caused abrupt pH decreases after the onset of ice crystallization, at temperatures between −0.5 and −4.0°C. Decreasing the initial buffer concentration and/or initial pH resulted in higher final pH values at −10°C, farther removed from the equilibrium value of 3.6. At an initial pH of 7.4, the 50 and 100 mM buffer solutions reached a pH of 4.2 ± 0.1 at −10°C, whereas the 8 mM solutions reached a pH of 5.2 ± 0.2. Solutions having an initial pH of 5.7 and initial buffer concentrations of 8 and 100 mM experienced less pH shifts upon freezing to −10°C, with final pH values of 5.1 ± 0.1 and 4.7 ± 0.1, respectively.
Conclusions. Precipitation-induced pH shifts are dependent on the concentrations (activities) of precipitating ions, and are determined by both initial pH and salt concentration. The ion activity product is a meaningful parameter when describing salt precipitation in solutions prepared by mixing salts containing precipitating and nonprecipitating ions.
- L. van den Berg. The effect of addition of sodium and potassium chloride to the reciprocal system: KH2PO4-Na2HPO4-H2O on pH and composition during freezing. Arch. Biochem. Biophys. 84:305-315 (1959).
- N. Murase and F. Franks. Salt precipitation during the freeze-concentration of phosphate buffer solutions. Biophys. Chem. 34:293-300 (1989).
- N. Murase, P. Echlin, and F. Franks. The structural states of freeze-concentrated and freeze-dried phosphates studied by scanning electron-microscopy and differential scanning calorimetry. Cryobiology 28:364-375 (1991).
- R. K. Cavatur and R. Suryanarayanan. Characterization of frozen aqueous solutions by low temperature X-ray powder diffractometry. Pharm. Res. 15:194-199 (1998).
- M. J. Pikal. Freeze-drying of proteins—Part II: Formulation selection. BioPharm. 4:26-30 (1990).
- M. W. Towsend and P. P. DeLuca. Use of lyoprotectants in the freeze-drying of a model protein, ribonuclease A. J. Parenter. Sci. Technol. 42:190-199 (1988).
- S. S. Larsen. Studies on stability of drugs in frozen systems IV: The stability of benzylpenicillin sodium in frozen aqueous solutions. Dansk. Tidsskr. Farm. 45:307-316 (1971).
- M. P. W. te Booy, R. A. de Ruiter, and A. L. J. de Meere. Evaluation of the physical stability of freeze-dried sucrose-containing formulations by differential scanning calorimetry. Pharm. Res. 9:109-114 (1992).
- L. van den Berg. pH changes in buffers and foods during freezing and subsequent storage. Cryobiology 3:236-242 (1966).
- S. S. Larsen. Studies on stability of drugs in frozen systems VI: The effect of freezing upon pH for buffered aqueous solutions. Arch. Pharm. Chem. Sci. Ed. 1:41-53 (1973).
- A. P. MacKenzie. Non-equilibrium freezing behaviour of aqueous systems. Phil. Trans. R. Soc. London. B 278:167-189 (1977).
- M. J. Taylor. Physico-chemical principles in low temperature biology. In B. W. W. Grout and G. J. Morris (eds.), The Effects of Low Temperatures on Biological Systems, E. Arnold, London, 1987, pp.1-71.
- A. E. Nielsen and J. M. Toft. Electrolyte Crystal Growth Kinetics. J. Cryst. Growth 67:278-288 (1984).
- I. López-Valero, C. Gómez-Lorente, and R. Boistelle. Effects of sodium and ammonium ions on occurrence, evolution and crystallinity of calcium phosphates. J. Cryst. Growth 121:297-304 (1992).
- O. Söhnel and J. Garside. Precipitation: Basic Principles and Industrial Applications, Butterworth-Heinemann Ltd., Oxford, 1992.
- H. Galster. pH Measurement, VCH, New York, 1991, pp.121-123.
- H. Galster. pH Measurement, VCH, New York, 1991, pp.156-162.
- W. Kurz and D. J. Fisher. Fundamentals of Solidification, Trans Tech Publications Ltd., Switzerland, 1986.
- A. E. Nielsen. Electrolyte crystal growth mechanisms. J. Cryst. Growth 67:289-310 (1984).
- R. Boistelle and J. P. Astier. Crystallization mechanisms in solution. J. Cryst. Growth 90:14-30 (1988).
- Y. K. Kharaka, E. H. Perkins, W. D. Gunter, and J. D. Debraal. Geochemical modeling of water-rock interactions using SOLMINEQ-88. 884227 US Geol. Surv. (1988).
- E. H. Perkins, Y. K. Kharaka, W. D. Gunter, and J. D. Debraal. Geochemical modeling of water-rock interactions using Solmineq-88. ACS Symp. Ser. 416:117-127 (1990).
- G. Gómez. Crystallization-Related pH Changes During Freezing of Sodium Phosphate Buffer Solutions, Ph.D. Thesis, University of Michigan, Ann Arbor, Michigan, 1995.
- C. Körber. Phenomena at the advancing ice liquid interface — solutes, particles and biological cells. Q. Rev. Biophys. 21:229-298 (1988).
- M. Kochs, C. Körber, B. Nunner, and I. Heschel. The influence of the freezing process on vapor transport during sublimation in vacuum-freeze-drying. Int. J. Heat Mass Transfer 34:2395-2408 (1991).
- M. Jochem, U. Hartman, and C. Korber. Modeling of coupled heat and mass transfer problem of nonplanar solidification and melting in aqueous solutions and numerical treatment. In K. D. Diller (ed.), Network Thermodynamics, Heat and Mass Transfer in Biotechnology, American Society of Mechanical Engineers, New York, 1987, pp.73-80.
- J. H. Perepezko. Kinetic processes in undercooled melts. Mater. Sci. Eng., A 226:374-382 (1997).
- S. Ganguly and K. S. Adiseshaiah. Ice nucleation in emulsified aqueous salt-solutions—A differential scanning calorimetry study. Colloids Surf. 66:105-111 (1992).
- D. Clausse, I. Sifrini, and J. P. Dumas. On the study by DSC of the unexpected ice melting at 0°C of emulsified aqueous saline solutions. Thermochim. Acta 122:123-133 (1987).
- R. J. Davey, A. M. Hilton, and J. Garside. Crystallization from oil in water emulsions: particle synthesis and purification of molecular materials. Chem. Eng. Res. Design 75:245-251 (1997).
- Effect of Initial Buffer Composition on pH Changes During Far-From-Equilibrium Freezing of Sodium Phosphate Buffer Solutions
Volume 18, Issue 1 , pp 90-97
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- salt precipitation
- pH changes
- phosphate buffers
- Industry Sectors