The novel formulation design of O/W microemulsion for improving the gastrointestinal absorption of poorly water soluble compounds.
The design of the novel O/W microemulsion formulation, which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds was examined. Using medium chain fatty acid triglyceride (MCT), diglyceryl monooleate (DGMO-C), polyoxyethylene hydrogenated castor oil 40 (HCO-40), ethanol and PBS (pH 6.8) as an oil phase, a lipophilic surfactant, a hydrophilic surfactant, a solubilizer and an aqueous phase, at the mixture ratio of 5%/1%/9%/5%/80% (w/w), respectively, the O/W microemulsion with an average particle diameter of 20 nm or less was prepared. Moreover, for nine kinds of poorly water soluble compounds, such as Ibuprofen, Ketoprofen, Tamoxifen, Testosterone, Tolbutamide and other new compounds, the solubility to water was increased from 60 to 20,000 times by this O/W microemulsion formulation. The AUCs in plasma concentration of Ibuprofen and a new compound, ER-1039, following single oral administration of these compounds as the O/W microemulsion to fasted rats were equivalent to that of solution administration or increased by nine and two times that of suspension administration, respectively. Accordingly, this novel O/W microemulsion is a useful formulation, which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds.
Araya
Hiroshi
H
Formulation Technology Research Department, Pharmaceutical Technology Division, Chugai Pharmaceutical Co. Ltd., 5-1, Ukima 5-chome, Kita-ku, Tokyo 115-8543, Japan. arayahrs@chugai-pharm.co.jp
Tomita
Mikio
M
Hayashi
Masahiro
M
D000818:Animals; D001682:Biological Availability; D002368:Castor Oil / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004075:Diglycerides / Q000737:chemistry; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry* / Q000494:pharmacology; D000431:Ethanol / Q000737:chemistry; D007052:Ibuprofen / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D009821:Oils / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D004075:Diglycerides; D004655:Emulsions; D009821:Oils; D014280:Triglycerides; D014867:Water; D000431:Ethanol; D002368:Castor Oil; D007052:Ibuprofen