A new approach to enhance oral bioavailability of Silybum Marianum dryextract: Association of mechanochemical activation and spray congealing

The aim of the work was to produce a delivery system for Silybum Marianum dry extract with enhancedoral bioavailability by combining two technologies (mechanochemical activation and spray congealing).Initially, the active was coground with sodium croscarmellose in a planetary mill in order to reach anactivated state more prone to dissolution. DSC, XRD, FT-IR and LD analyses showed the formation ofnanosized particles of dry extract, with reduced degree of crystallinity of the main crystalline flavolignans(silybine A and B). Then, microparticles containing the activated coground and, as comparison, thecorresponding physical mixture of extract and polymer and the dry extract alone were produced by spraycongealing technology using Gelucire® 50/13 as a hydrophilic low m.p. carrier. Microparticles containingthe activated coground were produced spherical in shape, achieved satisfactory yield and high encapsulationefficiency. These microparticles, in addition to a favourable in vitro solubilisation kinetic, in apreliminary in vivo study in five rats demonstrated their ability to improve very significantly the oralbioavailability of the main flavolignans of Silybum Marianum dry extract (silybin A and B). These resultssuggested that the association of mechanochemical activation and spray congealing could be consideredan innovative and very useful approach to the oral delivery of Silybum Marianum. Furthermore, for thefirst time the possibility of successfully applying the spray congealing technology for the preparation ofa herbal drug delivery system was shown.