Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 108, Issue 2, Pages 851-859Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2018.07.013
Keywords
Frovatriptan Succinate; intranasal; brain targetting
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The objective of the present study was to develop polymeric nanoparticles (PNPs) of frovatriptan succinate for brain targeting by nasal route. Double emulsion method was used to increase the entrapment efficiency of hydrophilic drug, and formulation was optimized by central composite design to achieve critical quality attributes namely particle size, zeta potential, and entrapment efficiency. Optimized batch was evaluated for surface morphology, in vitro release, permeation across nasal mucosa, stability, histopathology, and brain tissue uptake study. Prepared PNPs were found to be smooth with particle size of 264.4 +/- 0.04 nm, zeta potential -35.17 +/- 0.07mV, and 65.2 +/- 0.06% entrapment efficiency. PNPs showed biphasic release pattern, initial burst release followed by sustained release up to 72 h. Ex vivo diffusion study using goat nasal mucosa at pH 6.8 revealed that PNPs permeation across nasal mucosa was about 3 times more than the pure drug solution, and quick delivery of PNPs in brain region was confirmed by fluorescence microscopic evaluation in male Wistar rats after intranasal administration. Histopathology studies further revealed integrity of nasal mucosa after treatment with PNPs. The investigation indicated that hydrophilic drug, frovatriptan succinate can be successfully entrapped in PNPs to target brain via nasal delivery, and thus it could be an effective approach for nose to brain delivery. (c) 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.
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