A molecular orbital study on the chemical interaction across the indomethacin/silica interparticle boundary due to mechanical stressing

A discrete variational-Xα (DV-Xα) method was applied to elucidate the formation of C–O–Si bridging bonds, produced when a silanol group of SiO2 comes close enough to react with a carboxyl group of indomethacin (IM). A decrease in the coordination number (CN) of oxygen atoms per silicon atom at the SiO2 surface increased the net charge (NC) of the silanolic hydrogen atom and decreased the bond overlap population (BOP) between the silanolic oxygen and hydrogen atoms. These changes favored the formation and stabilization of C–O–Si bridging bonds with simultaneous dehydration. The computational results agreed well with our previous experimental study of a ground indomethacin–SiO2 mixture to obtain a better solid dispersion of the drug.