چکیده (انگلیسی):

This study reports on the effects that water absorbed into amorphous sodium indomethacin (NaIMC) can have on simultaneous tendencies to crystallize to its trihydrate form and to undergo base-catalyzed hydrolysis because of the plasticizing effects of water on molecular mobility. Meas-urement of water vapor absorption at 30°C and powder x-ray diffraction patterns as a function of relative humidity (RH) reveal that upon exposure to 21% RH, NaIMC does not crystallize over a 2-month period. Measurements of the glass transition temperature as a function of such exposure reveals a change in Tg from 121°C, dry, to 53°C at 21% RH, such that Tg at 21% RH is ~13°C above the highest storage temperature of 40°C used in the study. At 56% RH and higher, however, crystallization to the trihydrate occurs rap-idly; although over the 2-month period, crystallization was never complete. Assessment of chemical degradation by high-performance liquid chromatography analysis revealed significant instability at 21% RH; whereas at higher RH, the extent of chemical degradation was reduced, reflecting the greater crystallization to the more chemically stable crystal-line form. It is concluded that when amorphous forms of salts occur in solid dosage forms, the simultaneous effects of enhanced water vapor sorption on crystallization and chemi-cal degradation must be considered, particularly when as-sessing solid-state chemical degradation at higher tempera-tures and RH (eg, 40°C 75% RH).