Abstract
We evaluated the pharmacokinetics of silymarin solid dispersion in pigs to determine whether silybin bioavailability would be increased over that of a silymarin premix. In vitro dissolution testing was conducted using dissolution apparatus 1 (baskets) at 100 rpm at 37 ± 0.5°C in pH 1.2 HCl, pH 6.8 phosphate, and pH 4.3 acetate buffers containing 0.5% Tween-80. In vivo pharmacokinetics were studied using 16 healthy pigs (Yorkshire × Landrace) that were randomly assigned to two groups. Silymarin as solid dispersion and premix dosage forms were administered directly by stomach tubes at 50 mg kg−1 silybin. In vitro dissolution of silybin for the premix was 35.02, 35.90, and 38.70% in these buffers, respectively. In contrast, silybin dissolution in solid dispersions was increased to 82.92, 87.48, and 99.70%, respectively. Silymarin solid dispersion administered at a single dose resulted in a peak concentration (Cmax) of 1,190.02 ± 246.97 ng ml−1 with the area under the curve (AUC0−∞) at 1,299.19 ± 67.61 ng ml−1 h. These parameters for the premix groups were 411.35 ± 84.92 ng ml−1 and 586.82 ± 180.99 ng ml−1 h, respectively. The Cmax and AUC0−∞ values for the solid dispersion were about twice that of the premix and were consistent with the in vitro dissolution data.
Highlights
Silymarin represents a complex polyphenolic mixture extracted from the seeds of the milk thistle Silybum marianum L [1, 2] and is composed of 65–80% flavonolignans silybin, isosilybin, silychristin, and silydianin with trace amounts of flavonoids and 20–35% fatty acids and polyphenolics [3, 4]
The method used in this work was validated by adding silymarin to blank excipients from the solid dispersions and premix to 0.5, 1, and 10 μg ml−1 silybin
We found a cumulative release from silymarin solid dispersion prepared in HCl, phosphate, and acetate buffers containing Tween-80 that was about 2.5-fold greater than for the silymarin premix
Summary
Silymarin represents a complex polyphenolic mixture extracted from the seeds of the milk thistle Silybum marianum L [1, 2] and is composed of 65–80% flavonolignans silybin, isosilybin, silychristin, and silydianin with trace amounts of flavonoids and 20–35% fatty acids and polyphenolics [3, 4]. The main component of silymarin is silybin, synonymous with silibinin and is a mixture of two diastereomers A and B in an ∼1:1 proportion [6–8]. Radical scavenging, and metal chelating activities in vitro and in vivo that can inhibit neutrophil migration and reduce edema at sites of inflammation [9, 10]. Silymarin has potent effects against hepato-trophic viruses as well as those with other host ranges and is a potential broad-spectrum antiviral [12, 13]. Silymarin has an effect that allows its use in all of the most frequent causes of liver damage
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