The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion I: enhancing effects on oral bioavailability of poorly water soluble compounds in rats and beagle dogs.
We examined the design of the versatile novel self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion formulation which enhances the oral bioavailability by raising the solubility of poorly water soluble compounds. Namely, seven kinds of poorly water soluble compounds such as disopyramide, ibuprofen, ketoprofen, tolbutamide, and other new compounds, as the model compounds were used to compare the plasma concentration profile of the compound following single oral administration of each compound to rats and beagle dogs as a solution, an oily solution, a suspension (or a powder), an O/W microemulsion, and a SEDDS type O/W microemulsion. And the enhancing effect of the SEDDS type O/W microemulsion on the gastrointestinal absorption of these compounds was evaluated. In the components of the SEDDS type O/W microemulsion, medium chain fatty acid triglyceride (MCT), diglyceryl monooleate (DGMO-C), polyoxyethylene hydrogenated castor oil 40 (HCO-40), and ethanol were used as an oil, a lipophilic surfactant, a hydrophilic surfactant, and a solubilizer, at the mixture ratio of 25/5/45/25 (w/w%), respectively. Thereby, to six kinds of the model compounds except disopyramide, the solubility was from 340 to 98,000 times that in water, and the AUCs in plasma concentration of the compound were equivalent to that of solution or O/W microemulsion administration, or was increased by 1.5 to 78 times that of suspension administration. Accordingly, this novel SEDDS type O/W microemulsion is the versatile, 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., Tokyo, Japan. arayahrs@chugai-pharm.co.jp
Nagao
Shunsuke
S
Tomita
Mikio
M
Hayashi
Masahiro
M
D000818:Animals; D019540:Area Under Curve; D001572:Benzofurans / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D004285:Dogs; D016503:Drug Delivery Systems; D015195:Drug Design; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; C109755:AG-041R; D001572:Benzofurans; D004655:Emulsions; D007211:Indoles; D008055:Lipids; D013501:Surface-Active Agents; D007660:Ketoprofen; D007052:Ibuprofen