Structural Relaxation of Acetaminophen Glass

Abstract

The aim is to determine the structural stability of acetaminophen glass with time and temperature change, and to examine the merits of adapting the structural relaxation models of the glassy state for pharmaceuticals. Differential scanning calorimetry technique has been used to study the acetaminophen glass after keeping the samples for various periods at fixed temperatures and after keeping at various temperatures for fixed periods. A general formalism for thermodynamic changes during storage in a temperature fluctuating environment is given and the kinetics of the enthalpy and entropy decrease determined. At a fixed temperature, the decrease occurs according to a non-exponential kinetics. For the same storage time, but at different temperatures, the enthalpy and entropy decrease rises to a maximum value at a certain temperature and then declines. The peak appears at the temperature at which the internally equilibrated state of the sample is reached for a fixed storage time. The change in the normalized heat capacity during the heating of acetaminophen has been analysed in terms of a non-exponential, non-linear enthalpy relaxation model. A single set of parameters that fit the data for unannealed acetaminophen glass does not fit the calorimetric data for annealed glass. Since acetaminophen molecules form intermolecular hydrogen-bonds in the crystal state and likely to form such bonds more easily in the disordered state, effect of such bonds on structural relaxation is likely to be significant.