Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy

Int J Pharm. 2013 Jun 25;450(1-2):21-30. doi: 10.1016/j.ijpharm.2013.04.023. Epub 2013 Apr 20.

Abstract

Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.0% (w/v) soybean oil, 0.4% (w/v) α-asarone, 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68, and 2.2% (w/v) glycerol. The mean particle size of α-asarone-LE was 226±11 nm, the ζ-potential was -25.6±1.2 mV, the encapsulation efficiency was 99.2±0.1% and the drug loading efficiency was 3.45%. Stability, safety, and efficacy studies of α-asarone-LE were systematically investigated and compared to those of α-asarone-I. The α-asarone-LE not only showed a desired stability, but also exhibited excellent safety and improved efficacy in vivo, indicating its great potential for clinical application in the future.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allylbenzene Derivatives
  • Animals
  • Anisoles / administration & dosage*
  • Anisoles / chemistry
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / chemistry
  • Asthma / immunology
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Drug Hypersensitivity / etiology
  • Drug Stability
  • Ear / blood supply
  • Emulsions
  • Female
  • Guinea Pigs
  • Injections, Intravenous
  • Lecithins / chemistry*
  • Male
  • Mice
  • Polyethylene Glycols / chemistry*
  • Propylene Glycols / chemistry*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Soybean Oil / chemistry*
  • Toxicity Tests, Acute
  • Veins / drug effects
  • Veins / pathology

Substances

  • Allylbenzene Derivatives
  • Anisoles
  • Anti-Inflammatory Agents
  • Emulsions
  • Lecithins
  • PEO-PPO-PEO
  • Propylene Glycols
  • asarone
  • Polyethylene Glycols
  • Soybean Oil