Enhanced enteral bioavailability of vancomycin using water-in-oil-in-water multiple emulsion incorporating highly purified unsaturated fatty acid.
The aim of this study was to evaluate the potential of an emulsion incorporating unsaturated fatty acids to improve the mucosal absorption of poorly absorbed drugs from rat intestinal loops in situ, using a water-in-oil-in-water (W/O/W) multiple emulsion. Vancomycin hydrochloride (VCM) was used as a model drug with low oral bioavailability. The entrapment efficiency of VCM in the emulsion was approximately 60% and remained constant over storage for 1 month at 4 degrees C. The emulsion incorporating C18 unsaturated fatty acids or docosahexaenoic acid (DHA) markedly enhanced VCM absorption after colonic and rectal dosing. The effectiveness of DHA on VCM colonic absorption improvement was the same as that of oleic acid, and less than that of linoleic and linolenic acids. For rectal dosing, bioavailability was similar among various emulsions, in the range 40-50%. The effect of the emulsion incorporating oleic acid or DHA on improving VCM enteral bioavailability was not increased proportional to the incorporated amount. The electrical resistance of membranes was not changed by the incorporation of various fatty acids in emulsions. Our results indicated that W/O/W emulsions incorporating C18 unsaturated fatty acid or DHA were useful carriers for improving the absorption of poorly absorbable drugs via the intestinal tract without gross changes to tight junction function.
Kajita
M
M
Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Morishita
M
M
Takayama
K
K
Chiba
Y
Y
Tokiwa
S
S
Nagai
T
T
D000285:Administration, Rectal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003106:Colon / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000493:pharmacokinetics*; D004655:Emulsions; D005224:Fats, Unsaturated / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D019787:Linoleic Acid / Q000493:pharmacokinetics*; D008297:Male; D019301:Oleic Acid / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000378:metabolism*; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics*; D017962:alpha-Linolenic Acid / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D004655:Emulsions; D005224:Fats, Unsaturated; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D014640:Vancomycin; D019787:Linoleic Acid