Pharmaceutical Research

, Volume 21, Issue 5, pp 867–874 | Cite as

Effect of Aging on the Physical Properties of Amorphous Trehalose

Article

Abstract

Purpose. The purpose of this investigation was i) to study the effect of physical aging on crystallization and water vapor sorption behavior of amorphous anhydrous trehalose prepared by freeze-drying, and ii) to determine the effects of water sorption on the relaxation state of the aged material.

Methods. Freeze-dried trehalose was aged at 100°C for varying time periods to obtain samples with different degrees of relaxation. The glass transition temperature (Tg) and enthalpic relaxation were determined by differential scanning calorimetry, and the rate and extent of water uptake at different relative humidity values were quantified using an automated vapor sorption balance.

Results. Annealing below the Tg caused nucleation in the amorphous trehalose samples, which decreased the crystallization onset temperature on subsequent heating. However, no crystallization was observed below the Tg even after prolonged annealing. Physical aging caused a decrease in the rate and extent of water vapor sorption at low relative humidity values. Moreover, the water sorption removed the effects of physical aging, thus effectively causing enthalpic recovery in the aged samples. This recovery occurred gradually in the glassy phase and was not associated with a glass to rubber transition. We believe this aging reversal to be due to volume expansion during water sorption in the amorphous structure.

Conclusions. Thermal history of amorphous materials is a crucial determinant of their physical properties. Aging of amorphous trehalose led to nucleation below the Tg, and decrease in rate and extent of water sorption. Sorption of water resulted in irreversible changes in the relaxation state of the aged material.

aging amorphous trehalose crystallization nucleation below Tg relaxation water sorption 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

references

  1. 1.
    B. C. Hancock and G. Zografi. Characteristics and significance of the amorphous state in pharmaceutical systems. J. Pharm. Sci. 86:1–12 (1997).Google Scholar
  2. 2.
    D. Q. M. Craig, P. G. Royall, V. L. Kett, and M. L. Hopton. Relevance of the amorphous state to pharmaceutical dosage forms: Glassy drugs and freeze dried systems. Int. J. Pharm. 179:179–207 (1999).Google Scholar
  3. 3.
    J. J. Aklonis and W. J. MacKnight. Introduction to Polymer Viscoelasticity, John Wiley and Sons, New York, 1983.Google Scholar
  4. 4.
    L. Yu. Amorphous pharmaceutical solids: Preparation, characterization and stabilization. Adv. Drug Del. Rev. 48:27–42 (2001).Google Scholar
  5. 5.
    K. H. Illers. Influence of thermal history on the properties of poly(vinyl chloride). Makromol. Chem. 127:1–33 (1969).Google Scholar
  6. 6.
    A. H. C. Chan. Effect of Annealing Below the Glass Transition Temperature on Sorption and Transport of Carbon Dioxide in Polycarbonate. Ph.D. Thesis, University of Texas, 1978.Google Scholar
  7. 7.
    M. R. Tant and G. L. Wilkes. An overview of the nonequilibrium behavior of polymer glasses. Polym. Eng. Sci. 21:874–895 (1981).Google Scholar
  8. 8.
    L. C. E. Struik. Physical Aging in Amorphous Polymers and Other Materials, Elsevier, New York, NY, 1978.Google Scholar
  9. 9.
    L. C. E. Struik. In W. Brostow and R. D. Corneliussen (eds.), Failure of Plastics, Macmillan, New York, 1986, pp. 209–258.Google Scholar
  10. 10.
    S. L. Shamblin, B. C. Hancock, Y. Dupuis, and M. J. Pikal. Interpretation of relaxation time constants for amorphous pharmaceutical systems. J. Pharm. Sci. 89:417–427 (2000).Google Scholar
  11. 11.
    S. L. Shamblin, X. Tang, L. Chang, B. C. Hancock, and M. J. Pikal. Characterization of the time scales of molecular motion in pharmaceutically important glasses. J. Phys. Chem. B. 103:4113–4121 (1999).Google Scholar
  12. 12.
    A. Pyne, R. Surana, and R. Suryanarayanan. Crystallization of mannitol below Tg' during freeze-drying in binary and ternary aqueous systems. Pharm. Res. 19:901–908 (2002).Google Scholar
  13. 13.
    V. Andronis and G. Zografi. Crystal nucleation and growth of indomethacin polymorphs from the amorphous state. J. Non-Cryst. Solids 271:236–248 (2000).Google Scholar
  14. 14.
    Y. Li, J. Han, G. G. Z. Zhang, D. J. W. Grant, and R. Suryanarayanan. In situ dehydration of carbamazepine dihydrate: A novel technique to prepare amorphous anhydrous carbamazepine. Pharm. Dev. Technol. 5:257–266 (2000).Google Scholar
  15. 15.
    M. J. Pikal, A. L. Lukes, and J. E. Lang. Thermal decomposition of amorphous beta-lactam antibacterials. J. Pharm. Sci. 66:1312–1316 (1977).Google Scholar
  16. 16.
    H. R. Costantino, K. G. Carrasquillo, R. A. Cordero, M. Mumenthaler, C. C. Hsu, and K. Griebenow. Effect of excipients on the stability and structure of lyophilized recombinant human growth hormone. J. Pharm. Sci. 87:1412–1420 (1998).Google Scholar
  17. 17.
    H. R. Costantino, J. D. Andya, P.-A. Nguyen, N. Dasovich, T. D. Sweeney, S. J. Shire, C. C. Hsu, and Y.-F. Maa. Effect of mannitol crystallization on the stability and aerosol performance of a spray-dried pharmaceutical protein, recombinant humanized anti-IgE monoclonal antibody. J. Pharm. Sci. 87:1406–1411 (1998).Google Scholar
  18. 18.
    M. Gordon and J. S. Taylor. Ideal copolymers and the second-order transitions of synthetic rubbers. I. Non-crystalline copolymers. J. Appl. Chem. 2:493–500 (1952).Google Scholar
  19. 19.
    L. S. Taylor. Carbohydrates as Protein Stabilizing Agents. Ph.D. Thesis, University of Bradford, 1996.Google Scholar
  20. 20.
    J. F. Willart, A. De Gusseme, S. Hemon, G. Odou, F. Danede, and M. Descamps. Direct crystal to glass transformation of trehalose induced by ball milling. Solid State Commun. 119:501–505 (2001).Google Scholar
  21. 21.
    S. P. Ding, J. Fan, J. L. Green, Q. Lu, E. Sanchez, and C. A. Angell. Vitrification of trehalose by water loss from its crystalline dihydrate. J. Therm. Anal. 47:1391–1405 (1996).Google Scholar
  22. 22.
    K. J. Crowley and G. Zografi. Cryogenic grinding of indomethacin polymorphs and solvates: Assessment of amorphous phase formation and amorphous phase physical stability. J. Pharm. Sci. 91:492–507 (2002).Google Scholar
  23. 23.
    L. S. Taylor, A. C. Williams, and P. York. Particle size dependent molecular rearrangements during the dehydration of trehalose dihydrate. In situ FT-Raman spectroscopy. Pharm. Res. 15:1207–1214 (1998).Google Scholar
  24. 24.
    J. D. Hancock and J. H. Sharp. Method of comparing solid-state kinetic data and its application to the decomposition of kaolinite, brucite, and barium carbonate. J. Am. Ceram. Soc. 55:74–77 (1972).Google Scholar
  25. 25.
    B. C. Hancock and C. R. Dalton. Effect of temperature on water vapor sorption by some amorphous pharmaceutical sugars. Pharm. Dev. Technol. 4:125–131 (1999).Google Scholar
  26. 26.
    A. R. Berens and I. M. Hodge. Effects of annealing and prior history on enthalpy relaxation in glassy polymers. 1. Experimental study on poly(vinyl chloride). Macromolecules 15:756–761 (1982).Google Scholar
  27. 27.
    A. H. Chan and D. R. Paul. Influence of history on the gas sorption, thermal, and mechanical properties of glassy polycarbonate. J. Appl. Polym. Sci. 24:1539–1550 (1979).Google Scholar
  28. 28.
    A. R. Berens. Solubility of vinyl chloride in poly(vinyl chloride). Angew. Makromol. Chem. 47:97–110 (1975).Google Scholar
  29. 29.
    A. R. Berens. Effects of sample history, time, and temperature on the sorption of monomer vapor by PVC. J. Macromol. Sci. Phys. B14:483–498 (1977).Google Scholar
  30. 30.
    A. Saleki-Gerhardt, C. Ahlneck, and G. Zografi. Assessment of disorder in crystalline solids. Int. J. Pharm. 101:237–247 (1994).Google Scholar

Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  1. 1.Department of PharmaceuticsUniversity of MinnesotaMinneapolisUSA

Personalised recommendations