Pharmaceutical Research

, Volume 18, Issue 3, pp 267–273

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

  • Suneel Rastogi
  • Marek Zakrzewski
  • Raj Suryanarayanan

DOI: 10.1023/A:1011086409967

Cite this article as:
Rastogi, S., Zakrzewski, M. & Suryanarayanan, R. Pharm Res (2001) 18: 267. doi:10.1023/A:1011086409967


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 

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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