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 degreesC 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 Si-29 and C-13 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. (C) 2001 Elsevier Science B.V. All rights reserved.