Formulation optimization and bioavailability after oral and nasal administration in rabbits of puerarin-loaded microemulsion.
The main objective of the study was to investigate the efficacy of microemulsion (ME) to facilitate bioavailability of puerarin (PUE) after oral and nasal administration. The pseudo-ternary phase diagrams were constructed to screen the ME components and optimize the ME formulation. The optimized formulation for bioavailability assessment consisted of 20% Tween 80, 20% glycerin, and 1.6% ethyl oleate. The solubility (27.8 mg/mL) of PUE in ME was significantly improved compared to that (4.58 mg/mL) of crude PUE in water. The ME droplets were spherical with a mean particle diameter of 23.4 nm. After nasal (5 mg/kg) and oral (20 mg/kg) administration of a single dose of PUE as ME to fasted rabbits, the absolute bioavailability was 34.58% and 13.54%, respectively. It showed a shorter T(max) (0.75 h) for nasal administration than that (1.0 h) for oral administration of PUE-loaded ME. The C(max) of PUE-loaded ME was 0.55 μg/mL after nasal administration and 0.64 μg/mL after oral administration, respectively. The results showed that nasal administration might be a promising route to enhance the absorption of PUE in the form of ME.
Yu
Aihua
A
Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan 250012, China.
Wang
Haigang
H
Wang
Jiali
J
Cao
Fengliang
F
Gao
Yan
Y
Cui
Jing
J
Zhai
Guangxi
G
D000042:Absorption; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004339:Drug Compounding; D004655:Emulsions; D005990:Glycerol; D007529:Isoflavones / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D009829:Oleic Acids; D010316:Particle Size; D011136:Polysorbates; D011817:Rabbits; D012995:Solubility; D012997:Solvents; D013501:Surface-Active Agents; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
D004655:Emulsions; D007529:Isoflavones; D009829:Oleic Acids; D011136:Polysorbates; D012997:Solvents; D013501:Surface-Active Agents; D014665:Vasodilator Agents; D005990:Glycerol; C033180:ethyl oleate; C033607:puerarin