Does Dispersion Dominate over H-Bonds in Drug–Surface Interactions? The Case of Silica-Based Materials As Excipients and Drug-Delivery Agents

Abstract

Amorphous silica is widely employed in pharmaceutical formulations both as a tableting, anticaking agent and as a drug delivery system, whereas MCM-41 mesoporous silica has been recently proposed as an efficient support for the controlled release of drugs. Notwithstanding the relevance of this topic, the atomistic details about the specific interactions between the surfaces of the above materials and drugs and the energetic of adsorption are almost unknown. In this work, we resort to a computational ab initio approach, based on periodic Density Functional Theory (DFT), to study the adsorption behavior of two popular drugs (aspirin and ibuprofen) on two models of an amorphous silica surface characterized by different hydrophilic/hydrophobic properties due to different SiOH surface groups' density. Particular effort was devoted to understand the role of dispersive (vdW) interactions in the adsorption mechanism and their interplay with H-bond interactions. On the hydrophilic silica surface, the H-bond pattern of the Si-OH groups rearranges to comply with the formation of new H-bond interactions triggered by the adsorbed drug. The interaction energy of ibuprofen with the hydrophilic model of the silica surface is computed to be very close to the sublimation energy of the ibuprofen molecular crystal, accounting for the experimental evidence of ibuprofen crystal amorphization induced by the contact with the mesoporous silica material. For both surface models, dispersion interactions play a crucial role in dictating the features of the drug/silica system, and they become dominant for the hydrophobic surface. It was proved that a competition may exist between directional H-bonds and nonspecific dispersion driven interactions, with important structural and energetic consequences for the adsorption. The results of this work emphasize the inadequacy of plain DFT methods to model adsorption processes involving inorganic surfaces and drugs of moderate size, due to the missing term accounting for London dispersion interactions.

Experimental and first-principles IR characterization of quercetin adsorbed on a silica surface

“…Moreover, the presence of the additional moleculesurface H-bonds enhances the Lewis acidity of the preexisting silanol H-bonds in silica alone. Similar results have been observed elsewhere [37][38][39]. The IR spectra, especially at high range, allow a detailed classification of the peaks, thus shedding light onto some cloudy parts of the experimental IR spectra [11].…”

Large-Scale B3LYP Simulations of Ibuprofen Adsorbed in MCM-41 Mesoporous Silica as Drug Delivery System

“…This approach allows the treatment of drug adsorption in MCM-41 in the same way as for silica surfaces. 20 These six inner surfaces, hereafter named S1−S6, are defined in Figure 1, and they are viewed in more detail in Figure 3. As expected, in all cases the most prominent surface feature is represented by SiOH functionalities (silanols).…”

Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations

“…3: All molecules form H-bonds with the exposed silanols through their COOH functionalities (2-3 per monomer, depending on the case). Particularly, it has been found [12,13] that ringed motifs of general structure OH ibu -OH Si -(OH Si )-OH Si -OC ibu (OH Si refers to the silanol SiOH groups of the silica walls.) are common stabilizing features in such systems and are here present in 4 out of 7 configurations (HL-3,4,6,7).…”

“…Quantum-mechanical simulations can give some insight on the issue, by providing geometries of adsorption, energetics and by predicting experimental observables (e.g., infrared spectra). In the past years, we have extensively investigated the interaction between ibuprofen, as a model of all propionic acid derivatives, and silica, using both surface models [12] and a realistic model for the MCM-41 mesoporous material [13], also simulating the effect of air humidity on the system [14].…”