The effects of emulsifying agents on disposition of lipid-soluble drugs included in fat emulsion.
The uses for drug delivery systems of two soybean oil fat emulsions prepared with an emulsifying agent, phosphatidyl choline (PC) or Pluronic F-127 (PLU), were examined comparatively in vivo and in vitro. In the presence of lipoprotein lipase (LPL) in vitro, the mean particle size of the PLU emulsion changed less than that of the PC emulsion. The production of non-esterified fatty acid (NEFA) from the PLU emulsion in the presence of LPL was smaller than that from the PC emulsion. These in vitro results indicate that the PLU emulsion is more stable than the PC emulsion. Plasma NEFA concentration following intravenous administration of the emulsions decreased with time for the PC emulsion, but was kept lower and constant for the PLU emulsion, supporting the in vitro stability data. The order of plasma cyclosporine A (CsA) concentration following intravenous administration in the above two emulsions and the mixed solution of polyethylene glycol 400 (PEG) and dimethylamide (DMA) in rats was PLU emulsion>PC emulsion>PEG/DMA solution. The plasma concentration was maintained higher and tissue distribution lower for the PLU emulsion than for other formulations. The uptake of oil violet (OV) into the rat parenchymal cells from the PLU emulsion was approximately half that from the PC emulsion, but the uptake into the Kupffer cells was almost equal in both emulsions. In conclusion, these emulsifying agents can control plasma elimination and tissue distribution of lipophilic drugs included in the emulsion. The use of the emulsion formulation makes it possible to avoid side effects through the reduction of drug uptake into non-targeted tissues.
Suzuki
Yasuyuki
Y
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Japan.
Masumitsu
Yasushi
Y
Okudaira
Kazuho
K
Hayashi
Masahiro
M
D000818:Animals; D016572:Cyclosporine / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D004355:Drug Stability; D045703:Emulsifying Agents / Q000493:pharmacokinetics*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D008071:Lipoprotein Lipase / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D010316:Particle Size; D010713:Phosphatidylcholines / Q000493:pharmacokinetics; D020442:Poloxamer / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D045703:Emulsifying Agents; D005217:Fat Emulsions, Intravenous; D010713:Phosphatidylcholines; D020442:Poloxamer; D013024:Soybean Oil; D016572:Cyclosporine; D008071:Lipoprotein Lipase