Formulation and Characterization of Clozapine Nanosuspension as a Sublingual Film

Background: Clozapine (CLZ) is a potent antipsychotic drug that suppresses the symptoms of schizophrenia and mania. Clozapine falls into Class II (BCS); its poor bioavailability is attributed to low water solubility and an extensive first-pass effect. Objective: To prepare CLZ as a nanosuspension (NS) to improve its low water solubility and load it into a sublingual film to enhance oral bioavailability. Methods: CLZ nanosuspensions are prepared by the “solvent anti-solvent precipitation” method using Soluplus as a stabilizing agent. We evaluated the polydispersity index (PDI) and the particle size of the CLZ nanosuspension formulations. The optimized formula of CLZ nanosuspension is loaded directly onto a sublingual thin film, eliminating the need for freeze-drying for solidification by the solvent casting approach. The sublingual films were characterized by thickness, surface pH, folding endurance, disintegration time, and in vitro dissolution rate. Results: We selected the formula F1 sublingual film as the best, as it demonstrated a uniform thickness of 0.087mm, good flexibility, and a surface pH of 6.7. It disintegrated quickly in 13 seconds and had a faster in vitro dissolution rate (3 min) compared to the CLZ ordinary films. Conclusions: The results confirmed the success of CLZ NS as a sublingual thin film for dissolution rate enhancement, which may improve oral bioavailability.