Effects of Cogrinding with β-Cyclodextrin on the Solid State Fentanyl

Fentanyl base and beta-cyclodextrin (beta-CD) were coground at 1: 1 and 1: 2 molar ratios (fentanyl: beta-CD) and the physicochemical characteristics of the mixtures were studied using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), solid state C-13 nuclear magnetic resonance (NMR) spectroscopy and powder X-ray diffraction (PXRD) measurement. Additionally, portions of the coground samples were exposed to high relative humidity to investigate fentanyl and beta-CD interactions. The results of DSC and PXRD analyses indicate that the ground mixtures are in an amorphous state, and the FTIR measurements show hydrogen bonding interactions between fentanyl and beta-CD. Solid state C-13 NMR indicates that a fentanyl/beta-CD inclusion compound is formed in the humidified mixture. Furthermore, PXRD data from the humidified mixtures are similar to the PXRD patterns from the inclusion complex. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:5019-5029, 2010