Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics.
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.
Yao
J
J
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
Hou
L
L
Zhou
J P
JP
Zhang
Z Q
ZQ
Sun
L
L
D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005026:Ethylene Glycols; D005990:Glycerol / Q000031:analogs & derivatives; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008140:Lorazepam / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D012995:Solubility; D013501:Surface-Active Agents
D004655:Emulsions; D005026:Ethylene Glycols; D006993:Hypnotics and Sedatives; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; C000515:cremophor EL; C010111:carbitol; D008140:Lorazepam; D005990:Glycerol