Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers

• Published in: Journal of pharmaceutical sciences Vol. 98; no. 1; p. 215
• Main Authors: Voinovich, D, Perissutti, B, Magarotto, L, Ceschia, D, Guiotto, P, Bilia, A R
• Format: Journal Article
• Language: English
• Published: United States 01-01-2009
• Subjects: Animals; Biomechanical Phenomena - physiology; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - pharmacokinetics; Male; Plant Extracts - chemistry; Plant Extracts - pharmacokinetics; Polymers - chemistry; Polymers - pharmacokinetics; Rats; Rats, Sprague-Dawley; Silybum marianum - chemistry
• ISSN: 1520-6017
• DOI: 10.1002/jps.21417

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.