Synthesis of ibuprofen eugenol ester and its microemulsion formulation for parenteral delivery.
The purpose of this study was to investigate the possibility of parenteral delivery of poorly water-soluble lipophilic drugs using a phospholipid-based microemulsion system. Ibuprofen eugenol ester (IEE), a highly lipophilic compound, was synthesized from ibuprofen and eugenol, and isolated as an amorphous whitish solid with a melting point at 40.2+/-0.1 degrees C, which structure was confirmed by IR, 1H-NMR and MS spectra. A pharmaceutically acceptable microemulsion system using Miglyol 812, soybean phosphatidylcholine (SbPC) and poly (ethylene glycol) (660)-12-hydroxystearate (Solutol HS-15), and PEG400 and ethanol as oil phase, surfactants and cosurfactants, respectively, was presented and characterized in terms of stability, droplet size distribution (DSD) and their solubilization capacity of IEE. The solubility of IEE in the optimized microemulsion formulation consisting of 6.4% ibuprofen eugenol, 9.6% Miglyol 812, 6% SbPC, 6% HS-15, 8.4% PEG400, 3.6% ethanol and 60% distilled water (w/w) was about 21,000 times higher than that in water. The ibuprofen blood concentration after intravenous administration of microemulsions was determined and compared with that of ibuprofen solution. It was concluded that the presented microemulsion system might be a promising intravenous dosage form of poorly water-soluble lipophilic drugs.
Zhao
Xiuli
X
School of Pharmacy, Shenyang Pharmaceutical University. raura3687yd@163.com
Chen
Dawei
D
Gao
Ping
P
Ding
Pingtian
P
Li
Kexin
K
D000818:Animals; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D005054:Eugenol / Q000737:chemistry*; D005260:Female; D007052:Ibuprofen / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004655:Emulsions; D004952:Esters; D012997:Solvents; D014867:Water; D005054:Eugenol; D007052:Ibuprofen