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J Pharm Sci ; 108(9): 3082-3090, 2019 09.
Article in English | MEDLINE | ID: mdl-31077685

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/pharmacokinetics , Brain/metabolism , Drug Carriers/chemistry , Lipids/chemistry , Lurasidone Hydrochloride/pharmacokinetics , Nanoparticles/chemistry , Administration, Intranasal , Animals , Antipsychotic Agents/administration & dosage , Chemistry, Pharmaceutical , Drug Design , Humans , Lurasidone Hydrochloride/administration & dosage , Male , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Models, Chemical , Nanoparticles/ultrastructure , Particle Size , Rats , Rats, Wistar , Schizophrenia/drug therapy , Solubility , Surface Properties
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