Stability of amorphous indomethacin compounded with silica

The stability of indomethacin (IM) compounded with SiO₂ either by co-grinding or by melt-quenching was examined by recrystallization kinetics under the conditions 30 °C and 11% relative humidity. A decrease of the recrystallization rate with and without an appreciable induction period was observed in both compounds. Higher stability of amorphous IM compounded with SiO₂ was attained by prolonged co-grinding than by melt-quenching. This was explained by the stronger chemical interaction at the interface between IM and SiO₂ by co-grinding, as revealed by ²⁹Si and ¹³C solid state NMR. Incomplete co-grinding with the rest of the crystalline state, however, made the amorphous state appreciably unstable, since the remaining crystallites serve as seeds for recrystallization.