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.