Solid State Stability Studies of Model Dipeptides: Aspartame and Aspartylphenylalanine

• Published in: Journal of pharmaceutical sciences 1997-01, Vol.86 (1), p.64-71
• Main Authors: Leung, Suzanne S., Grant, David J.W.
• Format: Article
• Language: English
• Subjects: Aspartame - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; Dipeptides - chemistry; Drug Stability; General pharmacology; Kinetics; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; X-Ray Diffraction
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js960228d

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 intramo-lecular aminolysis of the type, solid → solid + gas. This reaction was observed for APM at 167–180°C with the liberation of methanol and for AP at 186–202°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 266kJ mol-1 for APM and 234kJ mol-1 for AP.