Deepak Bahl1, Robin H Bogner. 1. School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, USA.
Abstract
PURPOSE: To quantify the effects of the ratio of indomethacin to Neusilin US2 and the processing humidity on the amorphization kinetics, stability and nature of the interaction. MATERIALS AND METHODS: A porcelain jar mill with zirconia balls was used to affect conversion of the physical mixtures (48 g) of indomethacin and Neusilin US2 (in the ratios 1:1 to 1:5) to amorphous states at room temperature (25 degrees C) employing either 0% RH or 75% RH. The percent crystallinity in the samples was determined from ATR-FTIR scans chemometrically. The physical stability of these co-ground amorphous powders was evaluated at 40 degrees C/75% RH and 40 degrees C/0% RH. RESULTS: The lower the ratio of indomethacin to Neusilin US2, the faster is the amorphization during co-grinding. Higher humidity facilitates amorphization with a more pronounced effect at the lower ratio of indomethacin to Neusilin US2. There is further amorphization of some of the partially amorphized samples on storage at 40 degrees C/75% RH for 3 months. Hydrogen bonding and surface interaction between metal ions of Neusilin US2 and indomethacin can explain changes in the FTIR spectra. CONCLUSIONS: The processing humidity and the ratio of indomethacin to Neusilin US2 are important factors to be considered to affect amorphization during ball milling. Amorphous indomethacin can be stabilized by co-grinding with Neusilin US2.
PURPOSE: To quantify the effects of the ratio of indomethacin to Neusilin US2 and the processing humidity on the amorphization kinetics, stability and nature of the interaction. MATERIALS AND METHODS: A porcelain jar mill with zirconia balls was used to affect conversion of the physical mixtures (48 g) of indomethacin and Neusilin US2 (in the ratios 1:1 to 1:5) to amorphous states at room temperature (25 degrees C) employing either 0% RH or 75% RH. The percent crystallinity in the samples was determined from ATR-FTIR scans chemometrically. The physical stability of these co-ground amorphous powders was evaluated at 40 degrees C/75% RH and 40 degrees C/0% RH. RESULTS: The lower the ratio of indomethacin to Neusilin US2, the faster is the amorphization during co-grinding. Higher humidity facilitates amorphization with a more pronounced effect at the lower ratio of indomethacin to Neusilin US2. There is further amorphization of some of the partially amorphized samples on storage at 40 degrees C/75% RH for 3 months. Hydrogen bonding and surface interaction between metal ions of Neusilin US2 and indomethacin can explain changes in the FTIR spectra. CONCLUSIONS: The processing humidity and the ratio of indomethacin to Neusilin US2 are important factors to be considered to affect amorphization during ball milling. Amorphous indomethacin can be stabilized by co-grinding with Neusilin US2.
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