Buffered Nanoemulsion for Nose to Brain Delivery of Ziprasidone Hydrochloride: Preformulation and Pharmacodynamic Evaluation.

Abstract

The study was undertaken to develop buffered nanoemulsion of ziprasidone hydrochloride (fifth generation antipshychotic) and evaluate its potential for efficacious nose to brain delivery drug delivery in animal models. Homogeneous buffered ziprasidone nanoemulsions (BZNE) were prepared by aqueous (phosphate buffer, pH 8.0) titration method using capmul MCM, labrasol and transcutol as oil, surfactant and cosurfactant respectively. The NEs (F1-F8) were characterized for pharmaceutical characteristics (% transmittance, PDI value, Zeta potential, globule size, viscosity and diffusion coefficient) and F6 with mean globule size of 145.24 ± 4.75nm (PDI = 0.186 ± 0.40) and diffusion coefficient of 0.1901± 0.04cm2/min was thermodynamically stable and was developed as buffered mucoadhesive nanoemulsions. The buffered mucoadhesive NE (βmax = 0.57) that contained 0.5% by weight of chitosan (BZMNE) exhibited 1.79 times higher diffusion coefficient (0.3418 ± 0.03) than BZNE. Pharmacodynamic study confirmed the superiority of BZMNE over BZNE in locomotor activity test (p< 0.05) and paw test (p<0.05). Nasal ciliotoxicity study revealed the optimized BZMNE to be free from acute toxicity. Conclusively, a stable and efficacious buffered mucoadhesive NE of ziprasidone hydrochloride, that can be safely administered by intranasal route was developed.