The composites of amorphous vortioxetine (VXT) and ordered mesoporous silica were prepared. Three silica matrixes with different pore sizes were used here: Mobil Composition of Matter No.41 (MCM), Santa Barbara Amorphous No.15 (SBA), and mesostructured cellular foam (MCF). The amorphous composites behaved enhanced physical stability (303.15 K, 56.0 ± 0.4% RH) compared to bulk VXT amorphism. Interestingly, the physical stability of these amorphous composites showed a great difference. Amorphous VXT loaded in MCF crystallized within 1 week, while VXT-SBA composites could be stable over 3 months. The stability of VXT-MCM composites were somewhere in between. In addition, with VXT loading decreasing, the physical stability of confined amorphous VXT became better. Nitrogen adsorption measurements indicated that VXT molecules were adsorbed in SBA in a dispersive state while aggregated in MCM and MCF. VXT-VXT interactions in MCM could be stronger than that in SBA. 1H-13C solid-state nuclear magnetic resonance experiments demonstrated the weaker VXT-VXT interactions in SBA. The dispersive adsorption state and weak VXT-VXT interactions were benefit to the physical stability of amorphous VXT in SBA channels. In addition, dissolution profiles of confined amorphous VXT and bulk crystalline VXT were determined and the dissolution rate of VXT loaded in nanopores was faster than the latter.
Keywords: adsorption state; amorphous composites; dissolution profile; mesoscopic confinement; physical stability; vortioxetine.