The molecular mobility of supercooled amorphous indomethacin as a function of temperature and relative humidity.
OBJECTIVE
To determine the relaxation times of supercooled indomethacin as a function of temperature and relative humidity above Tg, and to analyze the results in the context of being able to predict such behavior at various storage conditions.


METHODS
Dielectric relaxation times were measured in the frequency domain (12 to 10(5) Hz) for amorphous indomethacin equilibrated at 0, 56, and 83% relative humidity. The heating rate dependence of Tg for dry supercooled indomethacin was measured with differential scanning calorimetry and used to determine relaxation times. The results were compared with previously published shear relaxation times and enthalpy recovery data.


RESULTS
Very good agreement was observed between dielectric and shear relaxation times, and those obtained from the heating rate dependence of the Tg, for dry indomethacin as a function of temperature above Tg. The introduction of water lowered the dielectric relaxation times of supercooled indomethacin without significantly affecting its fragility. The relaxation times below Tg, found to be lower than those predicted by extrapolation of the data obtained above Tg, were analyzed in the context of the Adam-Gibbs-Vogel equation.


CONCLUSIONS
The relaxation times of amorphous indomethacin obtained from the heating rate dependence of Tg were in good agreement with those obtained from shear and dielectric measurements, thus validating a relatively simple approach of assessing molecular mobility. The significant molecular mobility of amorphous indomethacin observed below Tg, and the significant plasticizing effects of sorbed water, help to explain why amorphous indomethacin crystallizes well below Tg over relatively short time scales.
Andronis
V
V
School of Pharmacy, University of Wisconsin-Madison, 53706, USA.
Zografi
G
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D006813:Humidity; D007213:Indomethacin / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin