Drug Delivery by Silica Mesoporous Materials as Revealed by Quantum Mechanical Investigation

Piero Ugliengo,aMassimo Delle Piane,aMarta Corno,aRoberto Dovesi,aAlfonso Pedoneb

aDipartimento di Chimica, University of Torino, Via P. Giuria 7 – 10125 Torino - Italy

bDipartimento di Chimica, Universityof Modena e Reggio Emilia, Italy

Amorphous silica is widely employed in pharmaceutical formulations both as a tableting, anti-caking agent and as a drug delivery system. Recently, several authors proposed mesoporous silica materials, such as MCM-41, as efficient supports for the controlled release of drugs. However, there is little information about the interactions between drugs and amorphous silica surfaces, especially at the atomic level. In this work, we used the CRYSTAL14 code1 to study the behavior of aspirin and ibuprofen on silica surfaces] and, for ibuprofen, within an atomistic model of MCM-41 system2. We adopted both PBE and B3LYP level of theory with double and triple-ζ polarized basis set. We run the massive parallel version of CRYSTAL14 on HPC architecture to handle the MCM-41 system envisaging more than 1000 atoms in the unit cell. To understand the role of dispersive (vdW) forces in the adsorption mechanism we adopted the a posteriori correction proposed by Grimme. All calculations have revealed that dispersion interactions play a crucial role in dictating the features of the drug/silica system. The free energy of adsorption in the MCM-41 model is negative (spontaneous process) only when the functional includes the dispersion contribution as described above. An important conclusion is that a subtle balance exists between specific and directional interactions like H-bonds and non-specific dispersion interactions, with relevant structural and energetic consequences. From the methodological point of view, this work shows that pure DFT methods like PBE and B3LYP are in serious error when dealing with adsorption processes involving adsorbates of medium/large size due to the missing dispersive term.

Left: The MCM-41 mesoporous 42x42x12 Å unit cell silica model. Right: MCM-41 in interaction with seven ibuprofen molecules adsorbed on the pore walls.

  1. Dovesi, R., et alCRYSTAL14 : A Program for the Ab Initio Investigation of Crystalline Solids.Int. J. Quantum Chem. 114, 1287 (2014).
  2. Delle Piane, M., Corno, M., Pedone, A., Dovesi, R. & Ugliengo, P.Large-Scale B3LYP Simulations of Ibuprofen Adsorbed in MCM-41 Mesoporous Silica as Drug Delivery System.J. Phys. Chem. C118, 26737 (2014).

X ORAL PRESENTATION (invited for a Progress Report talk)

☐ POSTER PRESENTATION