ABSTRACT
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).
Subject(s)
Drug Carriers/chemistry , Silybum marianum/chemistry , beta-Cyclodextrins/chemistry , Area Under Curve , Biological Availability , Biomechanical Phenomena/physiology , Chemical Phenomena , Crystallization , Desiccation , Drug Stability , Half-Life , Kinetics , Metabolic Clearance Rate , Particle Size , Plant Extracts/chemistry , Porosity , Powders , Silybin , Silymarin/chemistry , Silymarin/pharmacokinetics , Solubility , Spectroscopy, Fourier Transform Infrared , Spectrum Analysis, Raman , Surface Properties , Time Factors , X-Ray DiffractionABSTRACT
The SER spectra of 1H-indazole adsorbed on silver hydrosol were recorded in the 1800-100 cm(-1) and in the 3200-2800 cm(-1) regions. The SERS data were interpreted on the basis of previous vibrational assignments, with the help of the results of DFT calculations carried out using the 6-31G** basis. From the comparison of SER and normal Raman spectra it can be deduced that 1H-indazole is non-dissociatively adsorbed on metal surface and that it interacts with silver sol via nitrogen atoms and ring pi-system. The molecular plane assumes a tilted orientation with respect to the silver surface. The effect of varying the concentration of adsorbate was also evaluated. The observed changes of the relative intensities of some enhanced bands suggest that the molecule assumes a more tilted orientation upon lowering the concentration of the adsorbate.
