Design and Characterization of Niosomal In-Situ Gel for Enhanced Bioavailability of Chlorpromazine HCl in Schizophrenia

Introduction: Schizophrenia is a typical psychotic disorder, also known as a split mind disorder, characterized by symptoms like delusions, hallucinations, and lack of insight. Chlorproma-zine HCl is an antipsychotic medication commonly used to treat schizophrenia. The drug has an ex-tensive hepatic first-pass metabolism and poor bioavailability. In addition, it is poorly permeable, resulting from its hydrophilicity. Methods: A niosomal in-situ nasal gel loaded with chlorpromazine HCl was developed for brain delivery in the current study. The thin-film hydration method was used to formulate noisome, 32 randomized full factorial design was used for optimization. They were evaluated for in-vitro drug release, zeta potential, EE%, particle size, and shape and morphology. To create an in-situ gel, these noisome were subsequently incorporated into a Carbopol-934P and HPMC-K4M liquid gelling solu-tion. Results: The vesicle size ranged from 111.3 nm to 171.4 nm, with the optimized F5 batch having a zeta potential of -32.0 mV. Entrapment efficiency ranged from 74.71% to 91.78%, and cumulative percent release ranged from 83.83% to 95.61%. Ex-vivo studies showed 93.74% drug permeation through sheep nasal mucosa after 8 hours. Discussion: The nasal niosomal in-situ gel of chlorpromazine HCl offers a promising approach for targeted brain delivery in schizophrenia, improving drug retention and patient compliance. Its poten-tial for rapid relief makes it suitable for patients with poor oral absorption or compliance, and may help reduce hospital admissions during acute episodes. Conclusion: This research demonstrated that niosomes have the potential for intranasal delivery of Chlorpromazine HCl, offering advantages over conventional formulations.