Preparation and in vitro Evaluation of Intranasal Clozapine Microemulsion

Systemic drug delivery in schizophrenia is a major challenge, due to blood-brain barrier and P-glycoprotein, which drawback entry of drugs into the brain. Many researchers have reported that various nasal formulations such as microemulsions, nanoparticulates and microspheres can be used to transport drug molecules to central nervous system (CNS) via olfactory and trigeminal neural pathways.

In this study, Intranasal microemulsions of clozapine were prepared, by using different excipients such as oleic acid, Tween 80, and polyethylene glycol 400, to improve dissolution rate and bioavailability of hydrophobic clozapine, enhance its permeability to the brain, reduce the dose, which reduces side effects of patients.

The physio-chemical properties of the formulations were evaluated in terms of transparency, physical stability, drug release, drug content, pH, and viscosity.

In vitro release studies were performed using dialysis bags, and the interactions between the clozapine and the excipients were studied.

Microemulsions were evaluated using SEM, FTIR, DSC, and the effect of the concentration of Surfactant Co-surfactant mixture (Smix) on the rate of drug release was evaluated.

As a result, transparent Microemulsions with high transmittance and physical stability were prepared, pH values of the prepared formulations were, 5.23-5.7. All formulations provided sustained drug release, releasing most of their content over 24 hours. FTIR and DSC confirmed limited interactions between Clozapine and the used excipients.