Calorimetric investigation of the structural relaxation of amorphous materials: evaluating validity of the methodologies

Abstract

Although the potential advantages of the amorphous solid state is widely recognized among pharmaceutical researchers, its industrial applications have been mainly limited to freeze-dried injectable formulations where the amorphous form is naturally produced. Applications in oral dosage forms have been limited due, at least in part, to the poor state of knowledge regarding physical properties and stability of amorphous materials. Relaxation behavior is perhaps one of the most important physical characteristics of amorphous materials because relaxation kinetics are closely related to physical and chemical stability. Although recent developments in calorimetry methodology have facilitated detailed characterization of relaxation behavior, some experimental difficulties remain, and quantitative analysis of structural relaxation is still under development. This review focuses on the calorimetric investigation of the structural relaxation of drugs and excipients, and discusses the difficulties in the experimental evaluation of the relaxation time by those methods. We also present an original investigation of the impact of increases in relaxation time during an annealing experiment on the values of relaxation time, tau, and stretched exponential constant, beta, obtained from analysis of the experiment according to the Kohlraush-Williams-Watts kinetic model. Using results from a numerical simulation, we find that the values of tau and beta obtained from the data analysis are too large and too small, respectively, but the value of stretched relaxation time, tau(beta), remains reliable. The time dependence of the relaxation time is likely to play an important role in the non-Arrhenius behavior of pharmaceutical glasses.