An
ethyl laurate-based microemulsion system with
Tween 80 as
surfactant,
propylene glycol and
ethanol as cosolvents was developed for intranasal delivery of
diazepam. Phase behavior and solubilization capacity of the microemulsion system were characterized and in vivo nasal absorption of
diazepam from microemulsion formulations was investigated in rabbits. A single isotropic region, which is considered as a bicontinuous microemulsion, was found in the pseudo-ternary phase diagrams developed at various
Tween 80:
propylene glycol:
ethanol ratios. With the increase of
Tween 80 concentration, the microemulsion region area, microemulsion viscosity, and the amount of H(2)O and
ethyl laurate solubilized into the microemulsion system increased; however, the increase of
ethanol percentage produced opposite effects.
Diazepam, a practically water-insoluble
drug, displayed a high solubility of 41 mg/ml in a microemulsion consisting of 15%
ethyl laurate, 15% H(2)O, and 70% (w/w)
surfactant/cosurfactant (
Tween 80:
propylene glycol:
ethanol at 1:1:1 weight ratio). Nasal absorption of
diazepam from this microemulsion was found to be fairly rapid. At 2 mg/kg dose, the maximum
drug plasma concentration was arrived within 2-3 min, and the bioavailability (0-2 h) after
nasal spray compared with
intravenous injection was about 50%. These results suggest that this
ethyl laurate-based microemulsion may be a useful approach for the rapid-onset delivery of
diazepam during the
emergency treatment of
status epilepticus.