title: Silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability.
abstract: Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Ruyue
authors.initials: R
authors.lastname: Lian
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.forename: Yanan
authors.initials: Y
authors.lastname: Tan
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Niu
authors.forename: Peipei
authors.initials: P
authors.lastname: Guan
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004285:Dogs; D004337:Drug Carriers; D004339:Drug Compounding; D005989:Glycerides / Q000737:chemistry*; D050866:Liquid Crystals; D008297:Male; D008859:Microscopy, Polarization; D020442:Poloxamer / Q000737:chemistry*; D033362:Powder Diffraction; D020011:Protective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D012838:Silymarin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D005989:Glycerides; D020011:Protective Agents; D012838:Silymarin; D020442:Poloxamer; C005953:monoolein