Effects of Water Vapor Absorption on the Physical and Chemical Stability of Amorphous Sodium Indomet

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. Measurement
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 rapidly; 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 crystalline 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
chemical degradation must be considered, particularly when assessing
solid-state chemical degradation at higher temperatures and RH (eg,
40°C 75% RH).

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