Solid state mechanochemical activation of Silybum marianum dry extract with betacyclodextrins: Characterization and bioavailability of the coground systems.
Silybum marianum dry extract, whose therapeutic use is partially restricted by the insolubility in water of its main flavonolignans, was subjected to a mechanochemical activation process in planetary mill using betacyclodextrins as carriers. After optimization of the operating conditions according to an established theoretical model, the best active-to-carrier proportion was selected from the preliminary trials. When using the optimized conditions, the mechanochemical process permits an improvement of the physico-chemical properties of the active, which reaches an "activated" solid state, that is stable for at least 1 year. In fact, XRD, DRIFT and Raman spectroscopy analyses showed that the main extract component, Silybin, completely lost its crystalline structure after co-grinding with betacyclodextrins and formed weak interactions with the carrier. The powder characteristics remarkably changed after co-grinding, leading to a sample with a very small mean diameter and with a twofold increase of the specific surface area in comparison to the dry extract. The activated solid state of the coground systems remarkably enhanced the in vitro drug dissolution kinetics with consequent improved oral bioavailability. Furthermore, the in vivo studies on rats revealed a 6.6-fold bioavailability increase respect to the S. marianum Italian commercial product used as reference (Silirex 200 capsules).
Voinovich
D
D
Department of Pharmaceutical Sciences, University of Trieste, P.le Europa 1, I-34127 Trieste, Italy.
Perissutti
B
B
Grassi
M
M
Passerini
N
N
Bigotto
A
A
D019540:Area Under Curve; D001682:Biological Availability; D001696:Biomechanical Phenomena / Q000502:physiology; D055598:Chemical Phenomena; D003460:Crystallization; D003890:Desiccation; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006207:Half-Life; D007700:Kinetics; D008657:Metabolic Clearance Rate; D020944:Silybum marianum / Q000737:chemistry*; D010316:Particle Size; D010936:Plant Extracts / Q000737:chemistry; D016062:Porosity; D011208:Powders; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D013997:Time Factors; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D004337:Drug Carriers; D010936:Plant Extracts; D011208:Powders; D012838:Silymarin; D047392:beta-Cyclodextrins; D000077385:Silybin