Solid state stability studies of model dipeptides: aspartame and aspartylphenylalanine

Some solid-state pharmaceutical properties and the solid-state thermal stability of the model dipeptides aspartame (APM) and aspartylphenylalanine (AP), have been investigated. Studies by differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), high-performance liquid chromatography, powder X-ray diffraction, and optical microscopy have shown that the dipeptides undergo solid state intramolecular aminolysis of the type, solid --> solid + gas. This reaction was observed for APM at 167-180 degrees C with the liberation of methanol and for AP at 186-202 degrees C with the liberation of water. The exclusive solid product of the degradation reaction of both dipeptides is the cyclic compound 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine. The rates of the degradation reactions were monitored by isothermal TGA and by temperature-ramp DSC and were found to follow kinetics based on nucleation control with activation energies of about 266 kJ mol(-1) for APM and 234 kJ mol(-1) for AP.