Preparation and Evaluation of 2-(Allylthio)Pyrazine-Loaded Lipid Emulsion with Enhanced Stability and Liver Targeting

Abstract

To develop 2-(allylthio)pyrazine (2-AP)-loaded lipid emulsion for parenteral administration, various lipid emulsions were prepared with soybean oil, lecithin, and other carriers using homogenization method, and their physical stabilities were investigated by measuring their droplet sizes. The pharmacokinetics and tissue distribution of 2-AP in lipid emulsion after intravenous administration to rats were evaluated compared with 2-AP in solution. 2-AP was lipophilic, sparingly water-soluble, and unstable in aqueous medium. The 2-AP-loaded lipid emulsion composed of 1% of 2-AP, 4% of soybean oil, 4% of lecithin, and 91% of water was physically and chemically stable for at least 8 weeks. It gave significantly faster clearance of 2-AP and higher affinity to the organs, especially the liver, compared with the 2-AP in solution, suggesting that it could selectively deliver 2-AP to the liver. Thus, the lipid emulsion with soybean oil and lecithin could be used as a potential dosage form with the liver-targeting property and enhanced stability of sparingly water-soluble 2-AP.

Keywords:

• 2-(allylthio)pyrazine
• lipid emulsion
• stability
• pharmacokinetics
• liver-targeting

Acknowledgments

This work was financially supported by the Ministry of Education and Human Resources Development (MOE), the Ministry of Commerce, Industry and Energy (MOCIE), and the Ministry of Labor (MOLAB) through the fostering project of the Laboratory of Excellency.