Determination of the viscosity of an amorphous drug using thermomechanical analysis (TMA).
OBJECTIVE
To evaluate thermomechanical analysis (TMA) as a technique for determining the viscosity of amorphous pharmaceutical materials. This property of amorphous drugs and excipients is related to their average rate of molecular mobility and thus to their physical and chemical stability.


METHODS
Indomethacin was selected as a model amorphous drug whose viscosity has previously been reported in the literature. A Seiko TMA 120C thermomechanical analyzer was utilized in isothermal penetration mode to determine the viscosity of the amorphous drug over the maximum possible range of temperatures.


RESULTS
Using a cylindrical penetration geometry it was possible to accurately determine the viscosity of amorphous indomethacin samples by TMA over the temperature range from 35 to 75 degrees C. The results were consistent with those reported in the literature using a controlled strain rheometer over the range 44-75 degrees C. The limiting lower experimental temperature for the TMA technique was extended to significantly below the calorimetric glass transition temperature (Tg approximately 42 degrees C), thus allowing a direct experimental determination of the viscosity at Tg to be made.


CONCLUSIONS
Thermomechanical analysis can be used to accurately determine the viscosity of amorphous pharmaceutical materials at temperatures near and above their calorimetric glass transition temperatures.
Hancock
B C
BC
Merck Frosst Canada, Inc., Kirkland, Quebec. bruno_hancock@merck.com
Dupuis
Y
Y
Thibert
R
R
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002151:Calorimetry / Q000379:methods*; D005898:Glass; D007213:Indomethacin / Q000737:chemistry*; D012212:Rheology; D013696:Temperature; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin