4.5 Article

y Optimization of Nanostructured Lipid Carriers of Lurasidone Hydrochloride Using Box-Behnken Design for Brain Targeting: In Vitro and In Vivo Studies

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JOURNAL OF PHARMACEUTICAL SCIENCES
卷 108, 期 9, 页码 3082-3090

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2019.05.001

关键词

psychosis; nanostructured lipid carriers; lurasidone hydrochloride; intranasal; brain delivery; optimization; Box-Behnken design

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Intranasal nanostructured lipid carrier (NLC) of lurasidone hydrochloride (LRD) for brain delivery was prepared by the solvent evaporation method. The effects of independent variables, X1-lipid concentration, X-2 surfactant, and X-3 sonication times on dependent variables, Y1-particle size, Y-2 polydispersity index, and Y-3% entrapment efficiency were determined using Box-Behnken design. Optimized LRD-NLC was selected from the Box-Behnken design and evaluated for their morphological, physiological, nasal diffusion, and in vivo distribution in the brain after intranasal administration. Particle size, polydispersity index, and entrapment efficiency of optimized LRD-NLC were found to be 207.4 +/- 1.5 nm, 0.392 +/- 0.15, and 92.12 +/- 1.0%, respectively. Transmission electron microscopy and scanning electron microscopy was used to determine the particle size and surface morphology of LRD-NLC. The prepared LRD-NLC follows biphasic in vitro drug release. Prepared NLC showed a 2-fold increase in LRD concentration in the brain when compared with the drug solution following intranasal administration. Results showed that intranasal route can be a good and efficient approach for delivering the drug directly to the brain and enhancing the drug efficacy in the brain for the management of schizophrenia and a good alternative to oral drug delivery. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

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