title: Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers.
abstract: Simultaneous improvement of solubilization kinetics of main flavolignans of Silybum marianum extract was obtained cogrinding with two crosslinked polymers: micronized crospovidone, PVP-CL(R) and sodium carboxymethylcellulose, Ac-Di-Sol(R) in the 1:3 active-to-polymer weight ratio. By this process it was assessed that the main extract components lost its crystalline structure, and the powder surface area was increased by 2.1- and 1.7-fold in the coground products with Ac-Di-Sol(R) and PVP-CL(R), respectively. This activated status of the dry extract remained stable over a period of 2 years. Solubilization kinetics resulted ameliorated both in terms of entire dry extract and in terms of single components. When the 1/3 coground systems with PVP-CL(R) and Ac-Di-Sol(R) were dissolved in saturated conditions they gave a concentration improvement compared to the native product of 8 and 31 times of silybin A, 7 and 27 times of silybin B, whereas in the case of silychristin a double concentration was obtained only using Ac-Di-Sol(R). The in vivo studies on rats confirmed that this solubilization improvement corresponded to an effective oral bioavailability enhancement. The highest bioavailability improvement was obtained with Ac-Di-Sol(R), with a relative bioavailability of 88.6, 17.96, and 16.4 compared to the extract for silybin A, silybine B, and silychristine, respectively.
authors.affiliation: Department of Pharmaceutical Sciences, University of Trieste, P. le Europa 1, I-34127 Trieste, Italy. vojnovic@units.it
authors.forename: D
authors.initials: D
authors.lastname: Voinovich
authors.forename: B
authors.initials: B
authors.lastname: Perissutti
authors.forename: L
authors.initials: L
authors.lastname: Magarotto
authors.forename: D
authors.initials: D
authors.lastname: Ceschia
authors.forename: P
authors.initials: P
authors.lastname: Guiotto
authors.forename: A R
authors.initials: AR
authors.lastname: Bilia
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D020944:Silybum marianum / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003432:Cross-Linking Reagents; D010936:Plant Extracts; D011108:Polymers