Oral bioavailability of silymarin phytocomplex formulated as self-emulsifying pellets.
The objective of this study was to develop new solid self-emulsifying pellets to deliver milk thistle extract (silymarin). These pellets were prepared via extrusion/spheronisation procedure, using a self-emulsifying system or SES (Akoline MCM®, Miglyol®, Tween 80®, soy lecithin and propylene glycol), microcrystalline cellulose and lactose monohydrate. To select the most suitable formulations for extrusion and spheronisation, an experimental design of experiences was adopted. The screening amongst formulations (13 different blends) was performed preparing pellets and evaluating extrusion profiles and quality of the spheronised extrudates. The pellets were characterised for size and shape, density, force required to crush them. Although more than one type of pellets demonstrated adequate morphological and technological characteristics, pellets prepared from formulation 7 revealed the best properties and were selected for further biopharmaceutical investigations, including in vitro dissolution and in vivo trials on rats to study serum and lymph levels after oral administration of the pellets. These preliminary technological and pharmacokinetic data demonstrated that extrusion/spheronisation is a viable technology to produce self-emulsifying pellets of good quality and able to improve in vivo oral bioavailability of main components of a phytotherapeutic extract of more than 100 times by enhancing the lymphatic route of absorption.
Department of Pharmaceutical Sciences, University of Trieste, P. le Europa 1, I-34127 Trieste, Italy.
T
T
Iosio
D
D
Voinovich
B
B
Perissutti
F
F
Serdoz
D
D
Hasa
I
I
Grabnar
S Dall'
SD
Acqua
G P
GP
Zara
E
E
Muntoni
J F
JF
Pinto
D000818:Animals; D001682:Biological Availability; D045703:Emulsifying Agents; D004655:Emulsions; D020944:Silybum marianum / Q000737:chemistry*; D010936:Plant Extracts / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical
D045703:Emulsifying Agents; D004655:Emulsions; D010936:Plant Extracts; D012838:Silymarin