title: Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: design and evaluation.
abstract: Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance the solubility and oral bioavailability of oleanolic acid. The formulation design was optimized by solubility assay, compatibility tests, and pseudoternary phase diagrams. The morphology, droplet size distribution, zeta potential, viscosity, electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic acid were studied in detail. Compared with oleanolic acid solution, the in vitro release of oleanolic acid from SMEDDS showed that the drug could be released in a sustained manner. A highly selective and sensitive high-performance liquid chromatographymass spectrometry method was developed for determination of oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats. Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was achieved for the SMEDDS compared with the marketed product in tablet form. Our studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid via the oral route.
authors: Pharmacy Department, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
authors: Rui
authors: R
authors: Yang
authors: Xin
authors: X
authors: Huang
authors: Jinfeng
authors: J
authors: Dou
authors: Guangxi
authors: G
authors: Zhai
authors: Lequn
authors: L
authors: Su
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics*; D000431:Ethanol / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D009829:Oleic Acids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents; D014783:Viscosity
chemical_list: D004655:Emulsions; D009829:Oleic Acids; D013501:Surface-Active Agents; D000431:Ethanol; C000515:cremophor EL; D009828:Oleanolic Acid; D005990:Glycerol; C033180:ethyl oleate
keywords: bioavailability; formulation design; in vitro release; oleanolic acid; self-microemulsifying drug delivery system
references: Biopharm Drug Dispos. 2007 Mar;28(2):51-7
references: 17163409
references: Phytomedicine. 2003;10(6-7):483-9
references: 13678231
references: J Ethnopharmacol. 1995 Dec 1;49(2):57-68
references: 8847885
references: J Ethnopharmacol. 2003 Feb;84(2-3):299-305
references: 12648829
references: Pharm Res. 1995 Nov;12(11):1561-72
references: 8592652
references: Eur J Pharm Biopharm. 2006 Jul;63(3):288-94
references: 16527467
references: AAPS PharmSciTech. 2009;10(1):172-82
references: 19224372
references: Arch Pharm Res. 1997 Jun;20(3):269-74
references: 18975163
references: Phytomedicine. 2004 Feb;11(2-3):121-9
references: 15070161
references: Int J Pharm. 2008 May 1;355(1-2):269-76
references: 18242895
references: Phytochemistry. 2012 May;77:10-5
references: 22377690
references: Life Sci. 2004 Apr 16;74(22):2769-79
references: 15043991
references: Int J Pharm. 2004 Apr 15;274(1-2):65-73
references: 15072783
references: Fortschr Chem Org Naturst. 1998;74:1-196
references: 9597941
references: Biol Pharm Bull. 2006 Mar;29(3):508-12
references: 16508155
references: Planta Med. 2007 Feb;73(2):157-62
references: 17415876
references: AAPS PharmSciTech. 2007 Dec 21;8(4):E113
references: 18181534
references: Molecules. 2008 Dec 18;13(12):3224-35
references: 19104487
references: Toxicol Sci. 1998 Sep;45(1):88-93
references: 9848115
references: Nat Rev Drug Discov. 2007 Mar;6(3):231-48
references: 17330072
references: AAPS J. 2007 Oct 26;9(3):E344-52
references: 18170981
references: Crit Rev Food Sci Nutr. 1987;26(1):27-135
references: 3308321
references: J Pharm Pharmacol. 2005 Feb;57(2):259-64
references: 15720792
references: Phytochemistry. 2002 Jun;60(3):295-9
references: 12031449