Brain targeted intranasal in-situ gelling spray of paroxetine: Formulation, characterization and in-vivo evaluation

Purpose: of the research: Paroxetine is a medicine employed to treat major depression, social mental disturbances, panic and anxiety conditions etc. The high hepatic first pass effect of paroxetine leads to low oral bioavailability (<50%). Intranasal delivery of drug leads to bypassing of the first pass metabolism by direct delivery of a drug to the site of action i.e. brain. Thus, in-situ nasal gelling spray of paroxetine was formulated in the present investigation. Materials and methods: Pre-formulation studies were performed to evaluate an authenticity of drug and excipients and compatibility between them. In situ gel was formulated using ionic gelation technique. Hydroxypropyl beta-cyclodextrin was added to solubilize Paroxetine. Characterization was done to study total drug content, in-vitro release, ex-vivo (permeation and mucoadhesion) and histopathology. In-vivo pharmacokinetic and pharmacodynamic studies were done using rats. Results: The developed formulation was a clear solution with 99.29 +/- 2.03% drug content and 83.79 +/- 1.99% drug release in 6 h. The ex-vivo drug permeation study indicated 78.83 +/- 2.31% permeation in 6 h, while histopathology showed that the prepared formulation was non-toxic to nasal mucosa. The Cmax and Tmax obtained from the pharmacokinetic study were 870 +/- 9.72 ng/ml and 0.5 h respectively. Site specific delivery of Paroxetine to CNS results in quicker onset of action with increased accessibility at the target site and less systemic side effects. Conclusion: It can be concluded that the developed preparation has a faster onset of action with higher concentrations reaching the target site, i.e. brain.

Automated summary

The study demonstrated that intranasal gel spray delivery of paroxetine can increase the drug concentration in the brain and provide a quicker onset of action. Additionally, the formulation was found to be non-toxic to the nasal mucosa, showing potential as a new approach for treating depression and anxiety disorders.