Inclusion of ibuprofen by heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin: An X-ray diffraction and thermal analysis study

Inclusion of the non-steroidal anti-inflammatory drug ibuprofen by permethylated beta-cyclodextrin (TRIMEB) was investigated by thermal analysis and X-ray diffraction. Reaction between racemic ibuprofen and TRIMEB yielded a mixture of isomorphous crystals of TRLMEB - (R)-ibuprofen and TRIMEB - (S)-ibuprofen. The single crystal chosen for X-ray analysis was found to contain the (S)-isomer of the drug. The crystal is orthorhombic, space group P2(1)2(1)2(1), With a = 15.232(7) Angstrom, b = 21.327(7) Angstrom, c = 27.597(7) Angstrom and Z = 4. The structure was solved using the coordinates for the rigid portion of the cyclodextrin molecule of the isomorphous complex with (S)-naproxen. Refinement by full-matrix least-squares techniques gave a final R factor of 0.079 for 7473 unique observed reflections. The isobutyl group of(S)-ibuprofen is included in the cyclodextrin cavity through hydrophobic forces, with the propionic acid group protruding from the O(2), O(3) face. The lack of chiral discrimination of the host TRIMEB towards ibuprofen as guest was confirmed by a combination of X-ray diffraction methods, thermal analysis and polarimetry.