Anionic clays containing anti-inflammatory drug molecules: Comparison of molecular dynamics simulation and measurements

Three representative nonsteroidal anti-inflammatory drug molecules, Ibuprofen, Diclofenac, and Indomethacin, have been intercalated within the galleries of an anionic clay, Mg-Al layered double hydroxide (LDH). X-ray diffraction, IR and Raman vibrational spectroscopy and C-13 cross-polarization magic-angle spinning NMR have been used to characterize the confined drug molecules, while molecular dynamics (MD) simulations were used to probe the interlayer structure, arrangement, orientation, and geometry of the intercalated species. All three drug molecules are arranged as bilayers in the interlamellar space of the anionic clay. But while the structure of the intercalated lbuprofen is identical to that of the molecule outside the layers, spectroscopy as well as MD simulation shows that there is a change in the geometry of Diclofenac and Indomethacin upon confinement within the galleries of the LDH. The change in geometry of Diclofenac and Indomethacin upon intercalation is shown to originate from the electrostatic interaction between the electronegative chlorine atoms on the drug molecule and the positively charged metal hydroxide sheets of the anionic clay. It is shown that these changes in the geometry of the intercalated drug molecules allow for the observed interlayer spacing to be realized without the bilayers having to interdigitate, which would otherwise have been necessary if the structure of the drug molecules had remained identical to that outside the layers. Comparisons of experimental measurements with simulation have provided a more detailed understanding of the geometry and organization of flexible drug molecules confined in the anionic clay.