Design, Optimization and Evaluation of Intranasal Nanotherapeutic of Atypical Antipsychotic Drug

Abstract

Abstract Objective: The current study manifests the successful optimization and delivery of chitosan nanoparticles utilizing the nasal route to overcome inherent issues of ziprasidone hydrochloride, an atypical antipsychotic drug to curtail its bioavailability problems.Materials & Methods: Chitosan nanoparticles were prepared by ionic gelation technique and optimized using Box–Behnken design. In vitro drug release kinetics and ex vivo nasal permeation potential were determined.Results & Discussion: Chitosan nanoparticles exhibited a mean particle size of 153.8 ± 13.3 nm, a mean polydispersity index of 0.433 ± 0.15; an Entrapment Efficiency of 87.3 ± 3.62%, and a Drug loading capacity of 8.7 ± 0.25%. Transmission electron microscopy examinations revealed spherical particle size with uniform drug distribution. The physicochemical stability of nanoparticles was evaluated for 12 weeks, and they showed good stability at 25 ± 2°C/60 ± 5% RH. In vitro release studies established the supremacy of nanoparticles compared to drug suspension with cumulative drug release of 89.93% in pH 6.4 and 87.16% in pH 7.4. Ex vivo nasal permeation studies revealed a 5.26-fold increment in nasal permeation by nanoparticles, and the cumulative amount of drug permeated through nasal mucosa from nanoparticles was 2.58 ± 0.13 µg/cm2 × 10–2 compared to 1.02 ± 0.091 µg/cm2 × 10–2 from the drug suspension.Conclusion: Thus, in vitro and ex vivo results from nanoparticles showed remarkable potential in improving solubilization fate and nasal permeation of ziprasidone, thereby leading to prospective in vivo fate in enhancing brain delivery of ziprasidone.