Development of udenafil-loaded microemulsions for intranasal delivery: in vitro and in vivo evaluations.
To achieve rapid onset of action and improved bioavailability of udenafil, a microemulsion system was developed for its intranasal delivery. Phase behavior, particle size, transmission electron microscope (TEM) images, and the drug solubilization capacity of the microemulsion were investigated. A single isotropic region was found in pseudo-ternary phase diagrams developed at various ratios with CapMul MCM L8 as an oil, Labrasol as a surfactant, and Transcutol or its mixture with ethanol (1:0.25, v/v) as a cosurfactant. Optimized microemulsion formulations with a mean diameter of 120-154 nm achieved enhanced solubility of udenafil (>10mg/ml) compared with its aqueous solubility (0.02 mg/ml). An in vitro permeation study was performed in human nasal epithelial (HNE) cell monolayers cultured by the air-liquid interface (ALI) method, and the permeated amounts of udenafil increased up to 3.41-fold versus that of pure udenafil. According to the results of an in vivo pharmacokinetic study in rats, intranasal administration of udenafil-loaded microemulsion had a shorter T(max) value (1 min) compared with oral administration and improved bioavailability (85.71%) compared with oral and intranasal (solution) administration. The microemulsion system developed for intranasal administration may be a promising delivery system of udenafil, with a rapid onset of action and improved bioavailability.
College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Hyun-Jong
HJ
Cho
Wan-Sung
WS
Ku
Ubonvan
U
Termsarasab
Insoo
I
Yoon
Chung-Wook
CW
Chung
Hyun Tae
HT
Moon
Dae-Duk
DD
Kim
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D000431:Ethanol / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005989:Glycerides; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods; D000096926:Benzenesulfonamides
D004337:Drug Carriers; D004655:Emulsions; D000431:Ethanol; D005026:Ethylene Glycols; D005989:Glycerides; D009930:Organic Chemicals; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D012997:Solvents; D013449:Sulfonamides; C440220:Labrasol; C010111:carbitol; C419664:udenafil; D000096926:Benzenesulfonamides