Previous studies have shown that aspartame in the solid state can exis
t as a hemihydrate which occurs in two different polymorphic forms (I
and II). The present work shows that equilibration of either hemihydra
te at 25 degrees C with water vapor at relative humidities greater tha
n or equal to 58% or with liquid water produces a 2.5-hydrate. Upon su
bjecting each of these crystalline hydrates to increasing temperature,
the same crystalline anhydrate is formed which thermally cyclizes at
a higher temperature to form the known compound 3-(carboxymethyl)-6-be
nzyl-2,5-dioxopiperazine. The activation energy of the cyclization rea
ction appears to depend on the degree of crystallinity of the anhydrat
e that is formed at a lower temperature. On increasing the temperature
of the 2.5-hydrate, a hemihydrate intervenes before the anhydrate is
formed. This intervening hemihydrate is similar to the commercial form
(II) of aspartame hemihydrate but exhibits greater amorphous characte
r. The techniques employed were Karl Fischer titrimetry, powder X-ray
diffractometry, differential scanning calorimetry, thermogravimetric a
nalysis, solid-state C-13 nuclear magnetic resonance spectroscopy, and
Fourier transform infrared absorption spectroscopy.