Objective  To prepare asenapine maleate microemulsion gel (ASPM-Emulgel) and evaluate its brain targeting by nasal administration.

Methods  The prescription composition and dosage of asenapine maleate microemulsion (ASPM-Emul) was determined according to the equilibrium solubility of asenapine maleate (ASPM) in different oils, emulsifiers, co-emulsifiers and the compatibility results of excipients, and ASPM-Emul was prepared into a gel with carbomer 940 as the gel matrix. The particle size distribution and microstructure of ASPM-Emul were investigated. The in vitro release rates and permeability in sheep nasal mucosa of ASPM-Emul and ASPM Emulgel were compared using the Franz diffusion cell method. The nasal ciliary toxicity of ASPM-Emulgel was investigated using the in vivo toad maxillary model method. Brain targeting of ASPM-Emulgel by nasal administration in rats was evaluated.

Results  According to the results of equilibrium solubility and compatibility, Maisine 35-1, Tween 80 and Transcutol P were selected as the oil phase, emulsifier and co-emulsifier of ASPM-Emul, respectively, with the ratio of 4 ∶ 4 ∶ 2. ASPM-Emul was a light blue semi-transparent microemulsion with a particle size of (73.6±7.4) nm. The microemulsion was regularly spherical and uniformly dispersed under transmission electron microscopy. The results of in vitro release and permeation showed that the release rate of ASPM-Emul was relatively fast, while the release rate of ASPM-Emulgel remained stable. However, the permeability of the two formulations in sheep nasal mucosa was basically similar. ASPM-Emul and ASPM-Emulgel showed no significant toxicity to nasal cilia of toad. Compared with the tail vein ASPM group, the drug content in the brain of ASPM-Emul and ASPM-Emulgel significantly increased after nasal administration, both exhibiting significant brain targeting, and the drug targeting efficiency (DTE) of ASPM-Emulgel was higher.

Conclusion  The preparation of ASPM into microemulsion gel can significantly improve the brain targeting after nasal administration, and is expected to improve the clinical therapeutic effect of ASPM.

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