Structural arrangement and properties of layered double hydroxide drug nanocarrier intercalated by sulindac and mefenamic acid solved by molecular simulation methods

Molecular simulation methods were used for solving crystal structures and interlayer arrangements of layered double hydroxides intercalated with sulindac and mefenamic acid in its anionic form. Layered double hydroxides are used as biocompatible drug nanocarriers but the arrangement of intercalated species is not generally known. Calculated models showed that sulindac anions resp. mefenamic acid anions are anchored to layered double hydroxide layers by COO- groups with average space angle between drug anion and LDH surface of 56 degrees +/- 12 degrees resp. 14 degrees +/- 8 degrees, therefore both drug anions form so called bilayer arrangement in interlayer galleries. The sulfo groups on the opposite side of sulindac anion partially overlap each other in the middle of the interlayer, which is shown by the atomic density profiles. Bilayer arrangement of mefenamic acid anions is more strictly divided into two independent layers of drug anions. In both cases the water molecules together with Cl- anions are absorbed on layered double hydroxide surface. Calculated X-ray diffraction patterns reached good agreement with experimental ones and validated the resultant calculated models. Free volume analysis via Connolly surfaces method was employed in order to connect the structural properties of intercalates with the complexity of drug release process, thus the free volumes of the both intercalates were calculated and compared.