Milk Thistle (Silymarin) Bioavailability

[Right Hook]

I nabbed this from an anti-aging board:

Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches


The therapeutic indications mentioned above clearly indicates the potential of silymarin as a natural immunomodulator, but the problem with the use of silymarin lies in its poor bioavailability. Due to this reason the dose of silymarin given needs to be large so as to achieve therapeutic plasma levels. Various groups of scientists have used different approaches to address this problem and have succeeded in improving the bioavailability of silymarin.

Blumenthal et al . [90] has reported that the variation in silymarin absorption levels is generally between 20-50%. Several reasons have been attributed for this poor bioavailability, e.g., poor enteral absorption, [91],[92] degradation by gastric fluid, [90] or its poor solubility. [90],[93],[94],[95] This necessitates the incorporation of silymarin into a dosage form that can increase its delivery and hence its bioavailability. A number of studies have been reported in literature that were carried out to enhance the delivery of silymarin. These include complexation with cyclodextrin; [11],[96] incorporation in solid dispersion, [97],[98] which produced a 2-fold enhancement in the bioavailability of silymarin; [98] provision of silymarin in the form of salts of polyhydroxyphenylchromanones [93] and other more soluble derivatives; [99] or complexation with phospholipid. [51],[55],[94]

In order to improve the dissolution rate, Soo Woo et al . formulated silymarin in the form of a self-microemulsifying drug-delivery system (SMEDDS). [100] Based on pseudo-ternary phase diagram, the optimum formulation was obtained, consisting of 15% silymarin, 10% glyceryl monooleate as the oil phase, 37.5% mixture of polysorbate 20 and HCO-50 (1:1) as the surfactant, and 37.5% transcutol as the cosurfactant, with a surfactant/cosurfactant ratio of 1. The mean droplet size of the oil phase in the microemulsion was 67 nm. The release profile of silybin from the prepared SMEDDS capsule showed a significant increase in drug release over the reference capsule (Legalonβ). The percentage release of silybin from SMEDDS was 2.5 times higher than reference after 6 h. The pharmacokinetic evaluation of silymarin showed that there was an approximately 2-fold decrease in the t max from SMEDDS, 8-fold enhancement in the C max , and 3.6 times increase in the AUC, showing that there was a significant increase in the bioavailability of silymarin from SMEDDS over the conventional reference dosage form.

Abrol et al . studied the synergistic hepatoprotective effect of silymarin with phospholipids when encapsulated in microspheres to target the liver and compared the formulations with silymarin solution. [101] Various silymarin-loaded emulsions were formulated with soybean oil as the internal oily phase, soya lecithin as surfactant, and Tween 80 and propylene glycol as surfactant. In vitro release profile at 50 rpm showed an almost 4-fold increase in the release after 36 h compared to silymarin solution, indicating that the submicron range lipid emulsions help diffusing the drug in a more pronounced manner and thus increase the bioavailability of the drug. In vivo evaluation showed that there was significant reduction in phenobarbitone-induced sleep time (used as a measure of hepatoprotective activity) and reduction in enzymes (SGOT and SGPT) in rats receiving the microspheres as compared to those receiving the control or silymarin solution. Histopathological examination showed that there was almost complete protection of liver cells from carbon tetrachloride-induced intoxication with silymarin in lipid emulsion compared to plain lipid emulsion or silymarin solution. The above results show the positive impact of coupling silymarin with phospholipid in a microparticulate delivery system

To overcome the low bioavailablity of silymarin, Arcari et al . prepared an inclusion complex of silybin with b-cyclodextrin. This new complex was compared in in vitro tests (dissolution rate) and in an in vivo test (rat bile elimination) with silybin, silymarin, and one traditional formulation based on silybin. The results showed a dramatic increase in the dissolution rate of the complex (> 90% within 5 min) compared to the silybin, which is practically insoluble (< 5%). The in vivo results agree with the dissolution rates; after oral administration of the silybin complex, silybin concentration in the rat bile was nearly 20 times more than after administration of silybin as such or in a traditional formulation. In the last two cases, the silybin concentration was up to 6 times less than after administration of the same amount of silymarin. These data show that the b-cyclodextrin complexation could help in increasing the bioavailability of silybin. [11]

Yanyu et al . prepared silybin-phospholipid complexes to increase the bioavailability of orally administered silymarin and compared the pharmacokinetic characteristics and bioavailability after administration of silybin-phospholipid complex and silybin-N-methylglucamine in rats. [102] With ethanol as the reaction medium, silybin and phospholipid were dissolved in the organic medium and the solvent was removed under vacuum, which resulted in the formation of the complex. The solubility studies showed a 1000-fold increase in the solubility of the silybin complex in water and octanol compared to the solubility of the physical mixture. Dissolution of silybin complex at pH 6.8 was significantly more than at pH 1.2. At the end of 60 min the amount of silybin dissolved was 158.4 mg at pH 6.8 compared to 6.3 mg at pH 1.2. It was found that the rise in pH increased the dissolution of silybin. Rat bioavailability studies showed more than 5-fold enhancement in the bioavailability of silymarin from the phospholipid complex than the silybin-N-methylglucamine.

Yanyu et al . prepared silymarin proliposomes to increase the bioavailability of oral silymarin in beagle dogs. [103] The proliposomes were prepared by film-deposition of a silymarin and phospholipid mixture on a mannitol carrier in a round-bottom flask. Dissolution of proliposomes at pH 1.2 and 6.8 showed that the dissolution of silymarin was complete after 20 min, irrespective of the pH of the media. The dissolution of silymarin from the proliposomes was more than that from the control (silymarin-loaded mannitol powder prepared by same method as the proliposomes, but without the phospholipds). The encapsulation efficacy of the formulation was more than 90%, had a mean particle size of 196.4 nm, and was stable for 3 months at 40°C. The pharmacokinetic parameters for silymarin proliposomes and silymarin showed a t max of 30 min for both and C max of 472.62 and 89.78 ng/ml, and AUC of 2606.21 and 697 ng/ml, respectively, demonstrating enhanced GI absorption of silymarin from the proliposomes.

El-Samaligy et al . prepared the silymarin hybrid liposomes by reverse evaporation technique, using lecithin, cholesterol, stearyl amine, and tween 20 in a molar ratio of 9:1:1:0.5. [104] The prepared liposomes showed an encapsulation efficiency of 69.22%. Mixing silymarin-loaded liposomes with unloaded ones in 1:1 proportion was useful in the prevention of aggregates, which threaten liposomes stability. This selected formulation was stable with respect to encapsulation efficiency and particle size after 3 months of storage at 4°C. Differential scanning calorimetery and Fourier Transform Infrared spectroscopy gave evidence of silymarin and phospholipid interaction, which can help in enhancing permeation and hence the bioavailability of silymarin. In vivo studies using acute carbon tetrachloride administration produced a significant increase in serum SGPT level that was significantly reduced by the liposomal formulation and the silymarin suspension. The liposomal formulation significantly ( P < 0.001) reduced the SGPT level compared to suspension. Histopathological examination revealed similar effects with silymarin liposomes and suspension in the improvement of the necrosed area induced by carbon tetrachloride.

Wu et al . prepared a lipid-based SMEDDS, using ethyl linoleate (oil phase), tween 80 (surfactant), and ethanol (cosurfactant). [105] In vitro drug release studies carried out using the dialysis bag method showed the release of silymarin from SMEDDS as incomplete and having sustained characteristics. The relative bioavailability of SMEDDS was enhanced by an average of 1.88-fold and 48.82-fold from silymarin PEG 400 solution and suspension, respectively. The high bioavailability from the SMEDDS was attributed to its promotion of lymphatic transport [106] and the presence of long-chain oil, which promotes lipoprotein synthesis and subsequent lymphatic absorption.

More:
http://www.ijp-online.com/article.as...9;aulast=Dixit

[Right Hook]

Now I'm wondering if I should somehow supplement my cycle support with some sort of phospholipid. I need to look at that rat study closer...guessing it suspended in soy oil.

[Skigazzi]

I have been taking lecithin capsules with most of my supplements for the last couple years due to various studies showing phospholipids increases absorption, and a little extra choline never hurt anyone.

[TripDog]

I would read all that, but my ADD kicked in and I started day dreaming after the second sentence...plus I don't even think that is English anyway.

[Right Hook]

Originally Posted by Skigazzi

I have been taking lecithin capsules with most of my supplements for the last couple years due to various studies showing phospholipids increases absorption, and a little extra choline never hurt anyone.

I always buy generic lecithin capsules from my grocer. You using any good valued priced product?

Originally Posted by TripDog

I would read all that, but my ADD kicked in and I started day dreaming after the second sentence...plus I don't even think that is English anyway.

I heard Allessandra likes her men well read....too bad for you.

[Right Hook]

Originally Posted by Skigazzi

I have been taking lecithin capsules with most of my supplements for the last couple years due to various studies showing phospholipids increases absorption, and a little extra choline never hurt anyone.

I just saw that Primordial Performance has a new natty test booster coming out that delivers the active in a phospholipid matrix. If Eric is doing this with his products then you know it is something to look into...

[TripDog]

Originally Posted by Travis

I heard Allessandra likes her men well read....too bad for you.

Fuck you cracker, she loves my southpaw style, and my annaconda sized member........UGH!

[Right Hook]

Bump, anyone for suggestions on a good phospholipid product?

[LLLLern]

Milk Thistle