Molecular Mobility and Physical Stability of Amorphous Irbesartan

Amorphous systems have attracted considerable attention due to their favorable properties; however, their stability issues still pose a major challenge. The purpose of the present work was to investigate the role of molecular mobility and moisture in the physical stability of a selected pharmaceutical amorphous system. Irbesartan (IBS), a relatively stable glass, was chosen as the model drug, as it exhibits a good physical stability (resistance to crystallization) at temperatures below the glass transition (Tg-50 K). The amorphous system was annealed at temperatures 298 K (25 °C) and 313 K (40 °C) at 0 and 75 % RH to study the effect of temperature and moisture on its relaxation behavior. Differential scanning calorimetry (DSC) was used to characterize both the crystalline and the freshly prepared glass, and to monitor the extent of relaxation at temperatures below glass transition (Tg) as well as heat capacity changes as a function of temperature. Molecular relaxation time constant (τ) decreased drastically from 302 years to 68 hours with the increase in annealing temperature as determined by Kohlrausch-William-Watts (KWW) equation. IBS was found to be ‘relatively’ stable in the amorphous state and presented a challenge for temporal measurements. Hence, at low annealing temperatures, (T_g-50 K or below) initial relaxation time (τ⁰) was estimated using the calorimetric based approach. Amorphous IBS was non-hygroscopic and retained its glassy nature under the accelerated stability conditions. The extent of relaxation in the amorphous drug in the presence of moisture was also estimated.