Characterization of the time scales of molecular motion in pharmaceutically important glasses

Increased interest in molecular time scares below the glass transition temp erature, T-g, has arisen from the desire to identify the conditions (e.g., temperature) where the molecular processes which lead to unwanted changes i n amorphous systems (e.g., chemical reactivity, crystallization, structural collapse) are improbable. The purpose of this study was to characterize th e molecular mobility of selected amorphous systems (i.e., indomethacin, sor bitol, sucrose, and trehalose) below T-g using a combined experimental and theoretical approach. Of particular interest was the temperature where the time scales for molecular motion (i.e., relaxation time) exceed expected li fetimes or storage times. As a first approximation of this temperature, the temperature where the thermodynamic properties of the crystal and the equi librium supercooled liquid converge (i.e., the Kauzmann temperature, T-K) w as determined. T-K values derived from heat capacity and enthalpy of fusion data ranged from 40 to 190 K below the calorimetric T-g. A more refined ap proach, using a form of the Vogel-Tamman-Fulcher (VTF) equation derived fro m the Adam-Gibbs formulation for nonequilibrium systems below T-g, was used to predict the temperatures where the relaxation times of real glasses exc eed practical storage times. Relaxation times in glasses were characterized in terms of their fictive temperature, as determined from heat capacity da ta measured using modulated differential scanning calorimetry. The calculat ed relaxation times were in good agreement with measured relaxation times f or at least two materials. Relaxation times in real glasses were on the ord er of three years at temperatures near T-K, indicating low (but not zero) m obility under conditions where the equilibrium supercooled liquid experienc es total loss of structural mobility. The results of this study demonstrate the importance of excess configurational entropy formed during vitrificati on in determining structural relaxation dynamics in real glasses.