Intranasal Hydrogel of Armodafinil Hydroxypropyl-β-Cyclodextrin Inclusion Complex for the Treatment of Post-Traumatic Stress Disorder

The objective of the present study was to prepare and evaluate the therapeutic effect of armodafinil inclusion complex (AIC) hydrogel on Post-traumatic Stress Disorder.After computer simulation and physicochemical property investigation, the AIC was made by lyophilizing armodafinil with ethanol as solvent and hydroxypropyl-beta-cyclodextrin (HP-β-CD) aqueous solution. AIC hydrogel was prepared by adding AIC into methylcellulose hydrogel, and then assessed. The anti-PTSD efficacy of AIC was verified in animal experiments. Subsequently, the brain targeting of intranasal administration was evaluated by fluorescence imaging characteristics of Cy7 hydrogel in the nasal route of drug administration, pharmacokinetics and in-vivo distribution of armodafinil.The AIC encapsulation efficiency (EE) was (90.98±3.72) % and loading efficiency (LE) was (13.95±0.47) %. The high percentage of drug release and slow-release rate properties of AIC hydrogel was clarified by in-vitro release and rheological test. In animal experiment, PTSD mice in AIC Hydrogel group showed remarkable improvement in behavioral parameters and the biochemical indicators showed that AIC hydrogel had a protective effect on the brain tissue of PTSD mice. Fluorescence imaging intranasal administration of the drug had the characteristics of forming high local concentration at the same dose and had a better drug penetration potential. The drug targeting index (DTI) of AIC hydrogel nasal administration as to brains, compared to raw armodafinil gavage and AIC aqueous solution gavage, were calculated to be 1.62 and 2.39, respectively. AIC hydrogel is a promising formulation for the treatment of PTSD based on its high brain delivery and anti-PTSD effect.