Preparation, characterization, and optimization of asenapine maleate mucoadhesive nanoemulsion using Box-Behnken design: In vitro and in vivo studies for brain targeting.
Journalinternational journal of pharmaceutics4.845Date
2020 Jun 04
5 months ago
Journal Article
2020-Aug-30 / 586 : 119499
Kumbhar SA 1, Kokare CR 2, Shrivastava B 3, Gorain B 4, Choudhury H 5
  • 2. Department of Pharmaceutics, STES's Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India.
  • 3. School of Pharmaceutical Sciences, Jaipur National University, Jaipur 302017, Rajasthan, India. Electronic address: [email protected]
  • 4. School of Pharmacy, Faculty of Health and Medical Science, Taylor's University, 47500 Subang Jaya, Selangor, Malaysia.
  • 5. Department of Pharmaceutical Technology, School of Pharmacy, International Medical University, 57000 Kuala Lumpur, Malaysia. Electronic address: [email protected]
The tight junctions between capillary endothelial cells of the blood-brain barrier (BBB) restricts the entry of therapeutics into the brain. Potential of the intranasal delivery tool has been explored in administering the therapeutics directly to the brain, thus bypassing BBB. The objective of this study was to develop and optimize an intranasal mucoadhesive nanoemulsion (MNE) of asenapine maleate (ASP) in order to enhance the nasomucosal adhesion and direct brain targetability for improved efficacy and safety. Box-Behnken statistical design was used to recognize the crucial formulation variables influencing droplet size, size distribution and surface charge of ASP-NE. ASP-MNE was obtained by incorporating GRAS mucoadhesive polymer, Carbopol 971 in the optimized NE. Optimized ASP-MNE displayed spherical morphology with a droplet size of 21.2 ± 0.15 nm and 0.355 polydispersity index. Improved ex-vivo permeation was observed in ASP-NE and ASP-MNE, compared to the ASP-solution. Finally, the optimized formulation was found to be safe in ex-vivo ciliotoxicity study on sheep nasal mucosa. The single-dose pharmacokinetic study in male Wistar rats revealed a significant increase in concentration of ASP in the brain upon intranasal administration of ASP-MNE, with a maximum of 284.33 ± 5.5 ng/mL. The time required to reach maximum brain concentration (1 h) was reduced compared to intravenous administration of ASP-NE (3 h). Furthermore, it has been established during the course of present study, that the brain targeting capability of ASP via intranasal administration had enhanced drug-targeting efficiency and drug-targeting potential. In the animal behavioral studies, no extrapyramidal symptoms were observed after intranasal administration of ASP-MNE, while good locomotor activity and hind-limb retraction test established its antipsychotic activity in treated animals. Thus, it can be concluded that the developed intranasal ASP-MNE could be used as an effective and safe tool for brain targeting of ASP in the treatment of psychotic disorders.
Keywords: Antipsychotic activity Asenapine maleate Box-Behnken design Brain targeting potential Intranasal delivery Mucoadhesive nanoemulgel
Int J Pharminternational journal of pharmaceutics

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