Enhancing mechanism of intestinal absorption of highly lipophilic compounds using microemulsion – Quantitative analysis of the partitioning to the mesenteric lymph in intestinal cells

• Published in: Asian journal of pharmceutical sciences 2015-06, Vol.10 (3), p.186-193
• Main Authors: Iwanaga, Kazunori, Higashiyama, Yoichi, Miyazaki, Makoto, Kakemi, Masawo
• Format: Article
• Language: English
• Subjects: Intestinal absorption; Mesenteric lymph; Microemulsion; Partition; Quantitative analysis
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2014.12.005

The purpose of this study was to quantify the effect of the fatty acid alkyl-chain length of a polyethylene glycol (PEG) glyceryl ester, which was used as a microemulsion oil component, on the partitioning of highly lipophilic compounds to the mesenteric lymph after oral administration. Oil blue N, a highly lipophilic anthraquinone derivative, was orally administered to lymph duct-cannulated and untreated rats in two kinds of different microemulsions. Gelucire® 50/13 and Gelucire® 44/14 were used as the oil component with long chain and medium chain fatty acid portions, respectively, of PEG glyceryl esters in microemulsions. The cumulative amount of oil blue N in lymph fluid was almost the same between the two microemulsions, although the transferred amount of oil component (triglyceride) in the lymph after administration of the Gelucire® 50/13 microemulsion was significantly higher than that of the Gelucire® 44/14 microemulsion. On the other hand, the solubility of oil blue N in Gelucire® 44/14 was much higher than that in Gelucire® 50/13. No significant differences were observed between microemulsions in the bioavailability of oil blue N. From these data, the partitioning of oil blue N to the lymph was calculated using a mathematical model, showing that the partitioning ratios of oil blue N to the lymph fluid were almost the same for both microemulsions. The solubility of oil blue N to the oil component of the microemulsions and the transfer of triglycerides to the lymph after administration of the microemulsions counteract each other, leading to similar partitioning ratios of oil blue N to the lymph.