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 approximately 130 degrees C. ASA on further heating to approximately 180 degrees 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.
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 approximately 130 degrees C. ASA on further heating to approximately 180 degrees 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.
Authors: Niels Peter Aae Christensen; Bernard Van Eerdenbrugh; Kaho Kwok; Lynne S Taylor; Andrew D Bond; Thomas Rades; Jukka Rantanen; Claus Cornett Journal: Pharm Res Date: 2012-11-10 Impact factor: 4.200