Drug delivery mediated by silica based support: does dispersion dominate over H-bond interactions?

Amorphous silica is widely employed in pharmaceutical formulations both as a tableting, anti-caking agent and as a drug delivery system. Particularly, mesoporous silica materials, such as MCM-41, have been recently proposed as efficient supports for the controlled release of drugs. However, little information is known about the interactions between drugs and amorphous silica surfaces, especially at the atomic level. In this work we have applied a computational ab initio approach, exploiting the periodic Density Functional Theory (DFT), to study the adsorption behavior of two popular drugs (aspirin and ibuprofen) on silica surfaces. The CRYSTAL09 1 code was applied at PBE level of theory with a triple-ζ polarized basis set. Two silica models were adopted: one has a surface with 4.5 OH/nm 2 (hydrophilic character) and the other with 1.5 OH/nm 2 (hydrophobic). These two surface models are representative of two real surfaces treated at low (< 400°C) and high temperature (> 600°C), respectively. Particular importance was given to the study of the role of dispersive (vdW) forces in the adsorption mechanism by including the correction proposed by Grimme 2 . All calculations have revealed that adsorption of the considered drugs on silica surfaces is an exothermic process. In all considered cases dispersion interactions play a crucial role in dictating the features of the drug/silica system, and they are dominant for the highly dehydroxylated surface (see Figure). We have concluded that a subtle balance may exist between specific and directional interactions like H- bonds and non-specific dispersion interactions, with important structural and energetic consequences. From the methodological point of view, this work has shown that pure DFT methods are in serious error when dealing with adsorption processes due to the missing dispersive term. Case A – without dispersive contributions. Case B – with dispersive contributions. Figure Ibuprofen in interaction with the 1.5 OH/nm 2 highly dehydroxylated amorphous silica surface. 1 R. Dovesi, R. Orlando, B. Civalleri, C. Roetti, V. R. Saunders, C. M. Zicovich-Wilson, Z. Kristallogr., 2005, 220, 571-573 2 S. Grimme, J. Comput. Chem., 2006, 7(15), 1787-1799