Preparation and evaluation of 2-(allylthio)pyrazine-loaded lipid emulsion with enhanced stability and liver targeting.
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.
Jang
Jun-Hee
JH
Laboratory of Excellency for Drug and Gene Delivery, College of Pharmacy, Seoul National University, Seoul, South Korea.
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
Sung
Jung Hoon
JH
D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005217:Fat Emulsions, Intravenous / Q000737:chemistry*; D054709:Lecithins / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011719:Pyrazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry; D014018:Tissue Distribution
C104935:2-(allylthio)pyrazine; D004337:Drug Carriers; D004791:Enzyme Inhibitors; D005217:Fat Emulsions, Intravenous; D054709:Lecithins; D011719:Pyrazines; D013024:Soybean Oil