Pharmaceutical Research

, Volume 15, Issue 2, pp 194–199

Characterization of Frozen Aqueous Solutions by Low Temperature X-ray Powder Diffractometry

  • Raghu K. Cavatur
  • Raj Suryanarayanan
Article

Abstract

Purpose. A low temperature X-ray powder diffractometric (XRD) technique has been developed which permits in situ characterization of the solid-state of solutes in frozen aqueous solutions.

Methods. A variable temperature stage, with a working temperature range of −190 to 300°C, was attached to a wide-angle XRD. The stage was calibrated with a sodium chloride-water binary system.

Results. When aqueous nafcillin sodium solution (22% w/w) was frozen, eutectic crystallization of the solute was not observed. However, annealing at −4°C, caused crystallization of the solute. With increasing annealing time, there was a progressive increase in the crystallinity of the solute. Studies were carried out with sodium nafcillin solutions ranging in concentration from 20 to 50% w/w. The solid-state of the phase crystallizing from solution was independent of the solute concentration. Next, solutions of mono- and disodium hydrogen phosphate were individually frozen. Only the latter crystallized as the dodecahydrate (Na2HPO4⋅12H2O). However when an aqueous buffer mixture of mono- and disodium hydrogen phosphate was frozen, the former inhibited the crystallization of the latter.

Conclusions. Since freezing of solutions is the first step in lyophilization, the XRD technique can provide a mechanistic understanding of the alterations in solid-state that occur during freeze-drying. DSC has so far been the technique of choice to study frozen systems. The advantage of XRD is that it not only permits unambiguous identification of the crystalline solid phase(s), but it also provides information about the degree of crystallinity. While overlapping thermal events are difficult to interpret in DSC, XRD does not suffer from such a limitation.

low temperature X-ray powder diffractometry sodium nafcillin monosodium hydrogen phosphate disodium hydrogen phosphate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. 1.
    L. A. Trissel. Handbook of injectable drugs, ASHP, Bethesda, MD, 1994.Google Scholar
  2. 2.
    R. N. Chilamkurti. J. Parenter. Sci. Technol. 46:124–129 (1992).Google Scholar
  3. 3.
    M. J. Pikal. Biopharm 3:18–27 (1990).Google Scholar
  4. 4.
    L. R. Rey. Dev. Biol. Std. 36:19–29 (1977).Google Scholar
  5. 5.
    D. R. Savello and R. F. Shangraw. Am. J. Hosp. Pharm. 28:754–759 (1971).Google Scholar
  6. 6.
    P. Boutron and A. Kaufmann. J. Chem. Phys. 68:5032–5041 (1978).Google Scholar
  7. 7.
    L. G. Dowell, S. W. Moline, and A. P. Rinfret. Biochim. Biophys. Acta 59:158–167 (1962).Google Scholar
  8. 8.
    P. V. Hobbs. Ice Physics, Clarendon Press, Oxford, UK, 1974.Google Scholar
  9. 9.
    E. Ju. Shalev, D. V. Malakhov, A. N. Kanev, V. I. Kosyakov, F. V. Tuzikov, N. A. Varaksin, and V. I. Vavilin. Thermochim. Acta 196:213–220 (1992).Google Scholar
  10. 10.
    F. H. Cocks and W. E. Brower. Cryobiology 11:340–358 (1974).Google Scholar
  11. 11.
    Powder Diffraction File: Sets 29–30 and 42, Inorganic Databook (Editor-in-chief: W. F. McClune), International Centre for Diffraction Data, Swarthmore, PA, 1986 (Sets 29–30) and 1992 (Set 40).Google Scholar
  12. 12.
    N. Milton and S. L. Nail. Pharm. Dev. Technol. 1:269–277 (1996).Google Scholar
  13. 13.
    L. Gatlin and P. P. DeLuca. J. Parenter. Drug Assoc. 34:398–408 (1980).Google Scholar
  14. 14.
    Y. H. Roos. Phase Transitions in Foods, Academic Press, New York, 1995.Google Scholar
  15. 15.
    S. A. Evans, K. R. Morris, A. P. MacKenzie, and N. G. Lordi. J. Parenteral Sci. Technol. 49:2–8 (1995).Google Scholar
  16. 16.
    N. Murase and F. Franks. Biophys. Chem., 34:293–300 (1989).Google Scholar
  17. 17.
    T. Suzuki and F. Franks. J. Chem Soc. Faraday Trans. 89:3283–3288 (1993).Google Scholar
  18. 18.
    L. van den berg and D. Rose. Arch. Biochem. Biophys. 81:319–329 (1959).Google Scholar
  19. 19.
    G. Gomez. Crystallization-Related pH Changes During Freezing of Sodium Phosphate Buffer Solutions, Ph.D. Thesis, University of Michigan, 1996.Google Scholar
  20. 20.
    G. Gomez, N. Rodriguez-Hornedo, and M. J. Pikal. Pharm. Res. 11:S-265 (1994).Google Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Raghu K. Cavatur
  • Raj Suryanarayanan
    • 1
  1. 1.College of PharmacyUniversity of MinnesotaMinneapolis

Personalised recommendations