Influence of Adsorption State and Molecular Interaction on Physical Stability of Confined Amorphous Vortioxetine
Yun Cao1,2, Keke Zhang1,2, Mengwei Wang1,2
1School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin 300072, China.
Abstract:
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.
More Related Videos
Related Concept Videos
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Factors Influencing Drug Absorption: Pharmaceutical Parameters
Factors Influencing Drug Absorption: Physicochemical Parameters
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Physical Properties Affecting Solubility
As for any solution, the solubility of a gas in a liquid is affected by the attractive intermolecular forces between solute and solvent species. Unlike solid and liquid solutes, however, there is no solute-solute intermolecular attraction to overcome when a gaseous solute dissolves in a liquid solvent since the atoms or molecules comprising a gas are far separated and experience negligible interactions. Consequently, solute-solvent interactions are the sole...
Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model


