Stability of amorphous indomethacin compounded with silica.
The stability of indomethacin (IM) compounded with SiO(2) either by co-grinding or by melt-quenching was examined by recrystallization kinetics under the conditions 30 degrees 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 SiO(2) was attained by prolonged co-grinding than by melt-quenching. This was explained by the stronger chemical interaction at the interface between IM and SiO(2) by co-grinding, as revealed by (29)Si and (13)C 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.
Watanabe
T
T
Product Development Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. watatm@shina.sankyo.co.jp
Wakiyama
N
N
Usui
F
F
Ikeda
M
M
Isobe
T
T
Senna
M
M
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D007213:Indomethacin; D009682:Magnetic Resonance Spectroscopy; D012822:Silicon Dioxide
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012822:Silicon Dioxide; D007213:Indomethacin