The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion II: stable gastrointestinal absorption of a poorly water soluble new compound, ER-1258 in bile-fistula rats.
The stabilization effect of the novel self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion on the gastrointestinal absorption of a poorly water soluble new compound, ER-1258 was examined by bile-fistula model rats. In the components of this formulation, 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. The ratios of AUC in the non-treated rats to that in the bile-fistula rats were 5.1, 12.1 and 3.0 for the suspension, the oily solution and the SEDDS type O/W microemulsion, respectively. The risk from which the difference between individuals of the compound absorption amounts resulting from the flow of the bile secretion serves as the maximum was high in order of oily solution>suspension>SEDDS type O/W microemulsion. Therefore, it was verified that the SEDDS type O/W microemulsion was able to reduce this risk, compared with the other formulations. When short chain fatty acid triglyceride (Triacetin) was used as an oil, the similar effect was demonstrated in the formulation composed of sorbitan sesquioleate (SO-15) as a lipophilic surfactant and polyoxyethylene hydrogenated castor oil 60 (HCO-60) or polyoxyethylene 20 sorbitan monooleate (TO-10M) as a hydrophilic surfactant.
Araya
Hiroshi
H
Formulation Technology Research Department, Pharmaceutical Technology Division, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. arayahrs@chugai-pharm.co.jp
Tomita
Mikio
M
Hayashi
Masahiro
M
D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001658:Biliary Fistula / Q000378:metabolism*; D003137:Common Bile Duct Diseases / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000592:standards; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000592:standards; D007408:Intestinal Absorption; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D004655:Emulsions; D020847:Estrogen Receptor Modulators; D013501:Surface-Active Agents; D016572:Cyclosporine