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

Title: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

Volume: 15 Issue: 6

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

Affiliation:

• Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo,Egypt

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

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.

Cite this article as:

Abd-Elrasheed Eman, El-Helaly Nageeb Sara *, EL-Ashmoony M. Manal and Salah Salwa, 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, Current Drug Delivery 2018; 15 (6) . https://dx.doi.org/10.2174/1567201814666171130121732