Pharmaceutical Research

, Volume 18, Issue 3, pp 267–273 | Cite as

Investigation of Solid-State Reactions Using Variable Temperature X-Ray Powder Diffractrometry. I. Aspartame Hemihydrate

  • Suneel Rastogi
  • Marek Zakrzewski
  • Raj Suryanarayanan
Article

Abstract

Purpose. The object of this study was to demonstrate the applicability of variable temperature X-ray powder diffractometry (XRD) to investigate solid-state reactions using aspartame as a model compound.

Methods. Aspartame exists as a hemihydrate (ASH) under ambient conditions and converts to aspartame anhydrate (ASA) at ∼130°C. ASA on further heating to ∼180°C undergoes decomposition (intramolecular cyclization) to form a diketopiperazine derivative (DKP). The dehydration as well as the decomposition kinetics were studied isothermally at several temperatures. The unique feature of this technique is that it permits simultaneous quantification of the reactant as well as the product.

Results. While the dehydration of ASH appeared to follow first-order kinetics, the cyclization of ASA was a nucleation controlled process. The rate constants were obtained at various temperatures, which permitted the calculation of the activation energies of dehydration and cyclization from the Arrhenius plots. The activation energy of dehydration was also calculated according to the method described by Ng (Aust. J. Chem.,28:1169-1178, 1975) and the two values were in good agreement.

Conclusions. The study demonstrates that XRD is an excellent complement to thermal analysis and provides direct information about the solid-states of various reaction phases.

kinetics solid-state reaction X-ray powder diffractometry aspartame dehydration decomposition 

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REFERENCES

  1. 1.
    J. L. Ford and P. Timmins. Pharmaceutical Thermal Analysis: Techniques and Applications, Ellis Harwood Limited, Chichester, UK, 1993.Google Scholar
  2. 2.
    D. Giron. Themal analysis and calorimetric methods in the characterization of polymorphs and solvates. Thermochim. Acta. 348:1-59 (1995).Google Scholar
  3. 3.
    J. Han and R. Suryanarayanan. Influence of environmental conditions on the kinetics and mechanism of dehydration of carbamazepine dihydrate. Pharm. Dev. Tech. 3:587-596 (1998).Google Scholar
  4. 4.
    S. Rastogi, M. Zakrzewski, and R. Suryanarayanan. Use of high temperature X-ray powder diffractometry (XRD) to investigate complex solid-state reactions. Pharm. Res. 14:S192 (1997).Google Scholar
  5. 5.
    J. Nishijo and F. Takenaka. Studies of the properties of the complex medicines. I. Differential thermogravimetric analysis of aminophylline. J. Pharm. Soc. Jap. 99:824-829 (1979).Google Scholar
  6. 6.
    J. Nishijo, H. Minamiguchi, and R. Moriya. Solid complex of theophylline with trimethylenediamine. J. Pharm. Soc. Jap. 100:157-161 (1979).Google Scholar
  7. 7.
    N. V. Phadnis and R. Suryanarayanan. Polymorphism in anhydrous theophylline—Implications on the dissolution rate of theophylline tablets. J. Pharm. Sci. 86:1256-1263 (1997).Google Scholar
  8. 8.
    H. Hashizume, S. Shimomura, H. Yamada, T. Fujita, and H. Nakazawa. An X-ray diffraction system with controlled relative humidity and temperature. Powder Diffr. 11:288-289 (1996).Google Scholar
  9. 9.
    S. S. Leung and D. J. W. Grant. Solid state stability studies of model dipeptides: aspartame and aspartylphenylalanine. J. Pharm. Sci. 86:64-71 (1997).Google Scholar
  10. 10.
    R. D. Skwierczynski., Disorder, molecular mobility, and solid-state kinetics: the two-environment model. J. Pharm. Sci. 88:1234-1236 (1999).Google Scholar
  11. 11.
    S. S. Leung, B. E. Padden, E. J. Munson, and D. J. W. Grant. Solid state characterization of two polymorphs of aspartame hemihydrate. J. Pharm. Sci. 87:501-507 (1998).Google Scholar
  12. 12.
    S. S. Leung, B. E. Padden, E. J. Munson, and D. J. W. Grant. Hydration and dehydration behavior of aspartame hemihydrate. J. Pharm. Sci. 87:508-513 (1998).Google Scholar
  13. 13.
    P. L. Klug and L. E. Alexander. X-ray Diffraction Procedures for Polycrystalline and Amorphous Materials, Wiley, New York, 1974.Google Scholar
  14. 14.
    S. K. Rastogi, Phase Transitions and Decomposition Reactions in Pharmaceutical Solids. Ph.D. Dissertation, University of Minnesota, Minneapolis, MN, 2000.Google Scholar
  15. 15.
    J. H. Sharp, G. W. Brindley, and B. N. N. Achar. Numerical data for some commonly used solid state reactions. J. Am. Ceram. Soc. 52:781-791 (1963).Google Scholar
  16. 16.
    R. Suryanarayanan, Determination of the relative amounts of anhydrous carbamazepine (C15H12N2O) and carbamazepine dihydrate (C15H12N2O · H2O) in a mixture by powder X-ray diffractometry. Pharm. Res. 6:1017-1024 (1989).Google Scholar
  17. 17.
    C. Ahlneck and G. Zografi. Molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int. J. Pharm. 62:87-95 (1990).Google Scholar
  18. 18.
    J. T. Carstensen. Stability of solids and solid dosage forms, J. Pharm. Sci. 63:1-14 (1974).Google Scholar
  19. 19.
    W. Ng. Thermal decomposition in the solid state. Aust. J. Chem. 28:1169-1178 (1975).Google Scholar
  20. 20.
    P. Jacobs and F. Tompkins. Classification and theory of solid reactions. In G. Garner (ed.), Chemistry of the Solid-State, Academic Press, New York, 1955 pp. 184-212.Google Scholar
  21. 21.
    P. K. Gallagher and D. W. Johnson, Jr. The effects of sample size and heating rate on the kinetics of the thermal decomposition of CaCO3. Thermochim. Acta 6:67-83 (1973).Google Scholar
  22. 22.
    C. O. Agbada and P. York. Dehydration of theophylline monohydrate powder—Effects of particle size and sample weight. Int. J. Pharm. 106:33-40 (1994).Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Suneel Rastogi
    • 1
    • 2
  • Marek Zakrzewski
    • 3
    • 4
  • Raj Suryanarayanan
    • 1
  1. 1.College of PharmacyUniversity of MinnesotaMinneapolis
  2. 2.Forest Laboratories, Inc.Inwood
  3. 3.Philips Analytical X-rayAlmeloThe Netherlands
  4. 4.Advanced Solid State Characterization, Inc.Exton

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