Casein and acryl amide complexation and bio-adhesive polymeric nano micelles influence on vortioxetine dissolution, penetration enhancement and in vivo absorption

• Vortioxetine (VTX) is a new atypical antidepressant with low water solubility, oral absorption, and fast metabolism, VTX has been commercially manufactured and sold as a hydrobromide. • Two techniques were developed for dissolution, swelling, adherence, and penetration enhancements. The techniques were the VTX and casein (CAS) complexation using the maximum loading capacity, and VTX-polymeric nano micelle using the “Sandwich Technique”. • The study investigates the maximum binding capacity of VTX-CAS complex, its preparation, optimization, physiochemical characterizations, solubility assessment, VTX release analysis, swelling analysis, and mucus-penetrating study. • The study suggests that VTX-polymeric nano micelles, with their enhanced amorphic character and 91.10±16.34 nm size, could be an effective oral alternative to VTX hydrobromide therapy using several studies including the in vivo absorption and biocompatibility studies. Vortioxetine (VTX) is a new atypical antidepressant used to treat major depression and other mental disorders. Due to its low water solubility, oral absorption, and fast metabolism, VTX has been commercially manufactured and sold as a hydrobromide. Long-term VTX hydrobromide therapy is frequently associated with respiratory irritation and digestive dysfunction. Two techniques were developed for dissolution, swelling, adherence, and penetration enhancements. The techniques were the VTX and casein (CAS) complexation using the maximum loading capacity, and VTX-polymeric nano micelle using the “Sandwich Technique”. This study includes the maximum VTX-CAS binding capacity determination, VTX-CAS complex preparation, polymeric nano micelle encapsulating VTX-CAS complex optimizations, physiochemical characterisations, solubility assessment, VTX release analysis, swelling analysis and mucus-penetrating study of the VTX-CAS complex and VTX polymeric nano micelle in comparison to the VTX raw material. The optimum VTX-polymeric nano micelle dissolution, swelling, adherence, and penetration enhancements were supported by the results of 91.10±16.34 nm, +19 mV zeta-potential, structural arrangements, and enhanced amorphic character with the morphology and size distribution (50–100 nm). The VTX-polymeric nano micelle could serve as an oral alternative to the VTX hydrobromide therapy based on the results of the biocompatibility and in vivo absorption studies for the VTX-polymeric nano micellar system.