Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics

Pharmazie. 2009 Oct;64(10):642-7.

Abstract

The purpose of this study was to develop a microemulsion system for intranasal delivery of lorazepam. The phase behavior and properties of microemulsions were characterized in a pseudo-ternary system composed of Cremophor EL 35/Transcutol P/Lauroglycol FCC or Labrafil M 1944CS/water, and intranasal absorption of lorazepam from microemulsions was investigated in rabbit. The microemulsions, comprising of FCC, Cremophor EL 35/Transcutol P (1.5:1) and water, were optimal for intranasal delivery of lorazepam. These systems had a higher solubilization capacity with the particle size of <150 nm, and were stable at ambient conditions for at least six months. In vivo absorption studies showed that intranasal absorption of lorazepam from microemulsions at 0.38 mg/kg had the larger AUC(0-t), the longer half-life and the prolonged circulation time with the mean bioavailability of 80.84% for ME2 and 63.48% for ME8 as compared to the intramuscular injection at 0.16 mg/kg. These results indicate that microemulsions may bea promising approach for the intranasal delivery of lorazepam.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Emulsions
  • Ethylene Glycols
  • Glycerol / analogs & derivatives
  • Hypnotics and Sedatives / administration & dosage*
  • Hypnotics and Sedatives / chemistry
  • Hypnotics and Sedatives / pharmacokinetics*
  • Injections, Intramuscular
  • Lorazepam / administration & dosage*
  • Lorazepam / chemistry
  • Lorazepam / pharmacokinetics*
  • Particle Size
  • Pharmaceutical Vehicles
  • Rabbits
  • Solubility
  • Surface-Active Agents

Substances

  • Emulsions
  • Ethylene Glycols
  • Hypnotics and Sedatives
  • Pharmaceutical Vehicles
  • Surface-Active Agents
  • cremophor EL
  • carbitol
  • Lorazepam
  • Glycerol