Solid-state NMR study of ibuprofen confined in MCM-41 material

Ibuprofen (an anti-inflammatory drug that is a crystalline solid at ambient temperature) has been encapsulated in MCM-41 silica matrices with different pore diameters (35 and 116 angstrom). Its behavior has been investigated by magic angle spinning (MAS) H-1, C-13, and Si-29 solid-state NMR spectroscopy at ambient and low temperature. This study reveals an original physical state of the drug in such materials. At ambient temperature, ibuprofen is not in a solid state (crystalline or amorphous) and is extremely mobile inside the pores, with higher mobility in the largest pores (116 angstrom). The interaction between ibuprofen and the silica surface is weak, which favors fast drug release from this material in a simulated intestinal or gastric fluid. The quasi-liquid behavior of ibuprofen allows the use of NMR pulse sequences issued from solution-state NMR, such as the INEPT sequence, to characterize these solid-state samples. The solid-state MAS NMR study shows that the proton of the carboxylic acid group of ibuprofen is in a chemical exchange at ambient temperature. Furthermore, at low temperature (down to 223 K), NMR spectroscopy results show that ibuprofen is able to crystallize inside the largest pores (116 angstrom), whereas a glassy state is obtained for the smallest ones (35 angstrom).