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

• Published in: Phytomedicine (Stuttgart) Vol. 19; no. 2; pp. 160 - 168
• Main Authors: Passerini, N., Perissutti, B., Albertini, B., Franceschinis, E., Lenaz, D., Hasa, D., Locatelli, I., Voinovich, D.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 15.01.2012
• Subjects: Animals; Biological Availability; Calorimetry, Differential Scanning; Chemical Phenomena; Desiccation; Drug Carriers - chemistry; Drug Compounding; Drug Delivery Systems - methods; Fats - chemistry; Male; Mechanochemical activation; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Oils - chemistry; Oral bioavailability; Oral Sprays; Particle Size; Plant Extracts - chemistry; Powder Diffraction - methods; Rats; Rats, Wistar; Silybin; Silybum marianum - chemistry; Silybum Marianum dry extract; Silymarin - administration & dosage; Silymarin - blood; Silymarin - chemistry; Silymarin - pharmacokinetics; Solid lipid microparticles; Solubility; Spectroscopy, Fourier Transform Infrared; Spray congealing; Silybin; Oral bioavailability; Spray congealing; Solid lipid microparticles; Silybum Marianum dry extract; Mechanochemical activation
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2011.06.027

The combination of mechanochemical activation and spray congealing produces a delivery system with enhanced oral bioavailability of main flavolignans of Silybum Marianum dry extract, Silybin A and B. The aim of the work was to produce a delivery system for Silybum Marianum dry extract with enhanced oral 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 an activated state more prone to dissolution. DSC, XRD, FT-IR and LD analyses showed the formation of nanosized 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, the corresponding physical mixture of extract and polymer and the dry extract alone were produced by spray congealing technology using Gelucire ® 50/13 as a hydrophilic low m.p. carrier. Microparticles containing the activated coground were produced spherical in shape, achieved satisfactory yield and high encapsulation efficiency. These microparticles, in addition to a favourable in vitro solubilisation kinetic, in a preliminary in vivo study in five rats demonstrated their ability to improve very significantly the oral bioavailability of the main flavolignans of Silybum Marianum dry extract (silybin A and B). These results suggested that the association of mechanochemical activation and spray congealing could be considered an innovative and very useful approach to the oral delivery of Silybum Marianum. Furthermore, for the first time the possibility of successfully applying the spray congealing technology for the preparation of a herbal drug delivery system was shown.