title: Amorphization of Indomethacin by Co-Grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism.
abstract: 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.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, Connecticut 06269, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bahl
authors.forename: Robin H
authors.initials: RH
authors.lastname: Bogner
mesh_terms: 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
chemical_list: D017607:Aluminum Compounds; D000538:Aluminum Silicates; D017616:Magnesium Compounds; D017640:Silicates; C033065:aluminum magnesium silicate; D008274:Magnesium; D007213:Indomethacin