Preparation and evaluation of fexofenadine microemulsions for intranasal delivery.
To enhance the solubility and bioavailability of poorly absorbable fexofenadine, microemulsion system composed of oil, surfactant and co-surfactant was developed for intranasal delivery. Phase behavior, particle size, viscosity and solubilization capacity of the microemulsion system were characterized. Histopathology and in vivo nasal absorption of the optimized microemulsion formulations were also investigated in rats. A single isotropic region was found in the pseudo-ternary phase diagrams developed at various ratios with Lauroglycol 90 as oil, Labrasol as surfactant and Plurol Oleique CC49 or its mixture with PEG-400 (1:1) as cosurfactant. An increase in the microemulsion region in pseudo-ternary phase systems was observed with increased surfactant concentration. The optimized microemulsion formulations showed higher solubulization of fexofenadine, i.e., F1 (22.64 mg/mL) and F2 (22.98 mg/mL), compared to its intrinsic water solubility (1.51 mg/mL). Nasal absorption of fexofenadine from these microemulsions was found to be fairly rapid. Tmax was observed within 5 min after intranasal administration at 1.0 mg/kg dose, and the absolute bioavailability (0-4 h) was about 68% compared to the intravenous administration in rats. Our results suggested that these microemulsion formulations could be used as an effective intranasal dosage form for the rapid-onset delivery of fexofenadine
Piao
Hong-Mei
HM
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Balakrishnan
Prabagar
P
Cho
Hyun-Jong
HJ
Kim
Hyunjun
H
Kim
You-Sun
YS
Chung
Suk-Jae
SJ
Shim
Chang-Koo
CK
Kim
Dae-Duk
DD
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004655:Emulsions; D005989:Glycerides; D006018:Glycols / Q000737:chemistry; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism; D009821:Oils / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D014783:Viscosity
D004655:Emulsions; D005989:Glycerides; D006018:Glycols; D039563:Histamine H1 Antagonists, Non-Sedating; D009821:Oils; D009930:Organic Chemicals; D013501:Surface-Active Agents; C440220:Labrasol; D011092:Polyethylene Glycols; D016593:Terfenadine; C093230:fexofenadine