title: Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously.
abstract: Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions. However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate, an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC0-t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide, severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Xing
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China; School of Pharmacy, Fujian Medical University, University Town, Fuzhou 350108, PR China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: You
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Dongling
authors.initials: D
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Song
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, PR China. Electronic address: lsshhy@mail.sysu.edu.cn.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D001682:Biological Availability; D003513:Cycloheximide / Q000494:pharmacology; D003652:Decanoic Acids / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008208:Lymphatic System / Q000187:drug effects / Q000378:metabolism*; D009829:Oleic Acids / Q000737:chemistry*; D010894:Piroxicam / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
chemical_list: D003652:Decanoic Acids; D004655:Emulsions; D009829:Oleic Acids; D014280:Triglycerides; D010894:Piroxicam; D013024:Soybean Oil; D003513:Cycloheximide; C005830:tributyrin; C033180:ethyl oleate
keywords: Drug solubility; Ethyl oleate; Lymphatic absorption; Microemulsions; Piroxicam