Hydration and Dehydration Behavior of Aspartame Hemihydrate

Abstract

Previous studies have shown that aspartame in the solid state can exist as a hemihydrate which occurs in two different polymorphic forms (I and II). The present work shows that equilibration of either hemihydrate at 25 degrees C with water vapor at relative humidities > or = 58% or with liquid water produces a 2.5-hydrate. Upon subjecting 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-benzyl-2,5-dioxopiperazine. The activation energy of the cyclization reaction appears to depend on the degree of crystallinity of the anhydrate 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 character. The techniques employed were Karl Fischer titrimetry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, solid-state 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared absorption spectroscopy.

Solid-state NMR studies of pharmaceutical solids in polymer matrices

“…Bupivacaine-fb (free base) and bupivacaine-HCl have very different solid-state NMR spectra, indicating that the molecules of these compounds pack in unique crystal forms. These results are consistent with different crystalline forms of pharmaceutical compounds having unique solid-state NMR spectra [15,16,17,18,19,20,21,22,23,24,25,26]. The solid-state forms of bupivacaine in a tristearin matrix and in a matrix made of lipid, water, and protein were also investigated.…”

Dehydration kinetics of neotame monohydrate

“…6 Neotame also exists as solvates, such as a methanol solvate. 7 The related dipeptide, aspartame, exists as two crystalline polymorphic hemihydrates and as a crystalline bishemihydrate whose thermodynamic properties, including hydration, 8 dehydration, 8 polymorphic behavior, 9 and solid-state stability 10 have been studied extensively.…”

Solid-State Characterization of Two Polymorphs of Aspartame Hemihydrate

“…The hydration and dehydration behavior of aspartame will be discussed in a subsequent paper. 24 Polymorphic change affects the pharmaceutically important physical properties, such as melting point, solubility, dissolution rate, powder flow, and tableting behavior. Polymorphism of drugs and excipients has been extensively reviewed.…”