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

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. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association