Characterization of Medicinal Compounds Confined in Porous Media by Neutron Vibrational Spectroscopy and First-Principles Calculations: A Case Study with Ibuprofen

Abstract

Amorphous formulations of ibuprofen were prepared by confining the drug molecules into the porous scaffolds. The molecular interactions between ibuprofen and porous media were investigated using neutron vibrational spectroscopy. Ibuprofen was introduced into the pores using sublimation and adsorption method. Neutron vibrational spectra of both neat and confined ibuprofen were measured, and compared to the simulated ibuprofen spectra using first-principles phonon calculations. The neutron vibrational spectra showed marked difference between the neat crystalline and the confined ibuprofen in low-frequency region, indicating a loss of the overall structural order once the ibuprofen molecules were in the pores. Furthermore, the formation of ibuprofen dimers, which is found in the crystal structure, was greatly inhibited, possibly due to the preferential interactions between the carboxylic acid group of ibuprofen (-COOH) and the surface hydroxyl groups of porous scaffolds (Si-OH). The experimental evidence suggests that, at the current drug loading, most, if not all, of the confined ibuprofen molecules were bound to the pore surfaces via hydrogen bonding. The structural arrangement of ibuprofen in the pores appears to be monolayer coverage. In addition, neutron vibrational spectroscopy is proven an exceedingly useful technique to study adsorbent-adsorbate interactions.