Brain Targeted Intranasal Zaleplon Nano-emulsion: In-Vitro Characterization and Assessment of Gamma Aminobutyric Acid Levels in Rabbits’ Brain and Plasma at Low and High Doses

Author(s): Eman Abd-Elrasheed, Sara Nageeb El-Helaly*, Manal M. EL-Ashmoony, Salwa Salah.

Journal Name: Current Drug Delivery

Volume 15 , Issue 6 , 2018

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Graphical Abstract:


Background: Zaleplon is a pyrazolopyrimidin derivative hypnotic drug indicated for the short-term management of insomnia. Zaleplon belongs to Class II drugs, according to the biopharmaceutical classification system (BCS), showing poor solubility and high permeability. It undergoes extensive first-pass hepatic metabolism after oral absorption, with only 30% of Zaleplon being systemically available. It is available in tablet form which is unable to overcome the previous problems.

Objective: The aim of this study is to enhance solubility and bioavailability via utilizing nanotechnology in the formulation of intranasal Zaleplon nano-emulsion (ZP-NE) to bypass the barriers and deliver an effective therapy to the brain.

Method: Screening studies were carried out wherein the solubility of zaleplon in various oils, surfactants( S) and co-surfactants(CoS) were estimated. Pseudo-ternary phase diagrams were constructed and various nano-emulsion formulations were prepared. These formulations were subjected to thermodynamic stability, in-vitro characterization, histopathological studies and assessment of the gamma aminobutyric acid (GABA) level in plasma and brain in rabbits compared to the market product (Sleep aid®).

Results: Stable NEs were successfully developed with a particle size range of 44.6±3.4 to 136.9±1.6 nm.

Conclusion: A NE composed of 10% Miglyol® 812, 40% Cremophor® RH40 40%Transcutol® HP and 10% water successfully enhanced the bioavailability and brain targeting in the rabbits, showing a three to four folds increase than the marketed product.

Keywords: Zaleplon, intranasal nano-emulsion, in-vitro release, in-vivo studies, brain targeting, GABA measurement.

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Article Details

Year: 2018
Page: [898 - 906]
Pages: 9
DOI: 10.2174/1567201814666171130121732
Price: $65

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