Amorphization of Indomethacin by Co-Grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism.
OBJECTIVE
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.


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.
Bahl
Deepak
D
School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, USA.
Bogner
Robin H
RH
D017607:Aluminum Compounds; D000538:Aluminum Silicates / Q000737:chemistry*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D004339:Drug Compounding; D004355:Drug Stability; D006813:Humidity; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry*; D017616:Magnesium Compounds; D017640:Silicates; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D017607:Aluminum Compounds; D000538:Aluminum Silicates; D017616:Magnesium Compounds; D017640:Silicates; C033065:aluminum magnesium silicate; D008274:Magnesium; D007213:Indomethacin