Preparation and Evaluation of Silymarin β-cyclodextrin Molecular Inclusion Complexes.
01 Jul 2011-Journal of Young Pharmacists (No longer published by Elsevier)-Vol. 3, Iss: 3, pp 205-210
TL;DR: The aim of the present study is to improve the solubility and dissolution rate and in turn the hepatoprotective activity of the drug, by formulating its inclusion complex with beta (β)-cyclodextrin, using different methods.
About: This article is published in Journal of Young Pharmacists.The article was published on 2011-07-01 and is currently open access. It has received 96 citations till now. The article focuses on the topics: Solubility & Cyclodextrin.
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TL;DR: How novel techniques have achieved products with greater commercial viability and efficacy than their conventional counterparts is highlighted, especially pertinent in a market where an informed consumer demands an innovative all-in-one product that does not compromise in its results.
129 citations
TL;DR: To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract.
Abstract: Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from milk thistle (Silybum marianum) seeds, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, although clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.
100 citations
Cites methods from "Preparation and Evaluation of Silym..."
...[57] Freeze-drying Complex with HP-CD Kellici et al....
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TL;DR: It can be concluded that phytochemicals have multiple biological activities with broader safety index and improvement of their solubility will be truly beneficial to aid their effective delivery in healthcare.
77 citations
TL;DR: In conclusion, in vitro data are useful as a first indication for potential pharmacokinetic drug interactions with CAM, but the discrepancies between in vitro and clinical results for milk thistle and P. ginseng show that clinical studies are required for confirmation of potential interactions.
76 citations
TL;DR: Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin and it was found that both formulations entered into Caco-2 cells via energy-dependent mechanisms.
Abstract: Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.
63 citations
Cites background from "Preparation and Evaluation of Silym..."
...To overcome these drawbacks, in particular the low aqueous solubility and limited oral bioavailability, several strategies were employed in recent years, including complexation with phospholipids (phytosomes) [17], inclusion complex with -cyclodextrins [18], solid dispersions [19], microparticles [20], polymeric nanoparticles [21], liposomes [22], solid lipid nanoparticles [23], nanostructured lipid carriers [24], micro-/nanoemulsions [25,26], self-microemulsifying drug delivery systems [27] and polymeric micelles [28,29]....
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References
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TL;DR: The effects of substitution on various cyclodextrins properties and the forces involved in the drug-cyclodextrin complex formation are discussed, and methods which are useful in the optimization of complexation efficacy are reviewed.
2,124 citations
Book•
01 Jan 1993
TL;DR: Part 1 Monographs on drugs and ancillary substances, Supplementary drugs and other substances, and Indexes - directory of manufacturers.
1,788 citations
"Preparation and Evaluation of Silym..." refers background in this paper
...It is also reported to be effective in certain cancers.[1-5] The poor aqueous solubility of the drug may lead to dissolution-related bioavailability problems....
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TL;DR: It is concluded that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis and has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published.
Abstract: The high prevalence of liver diseases such as chronic hepatitis and cirrhosis underscores the need for efficient and cost-effective treatments. The potential benefit of silymarin (extracted from the seeds of Silybum marianum or milk thistle) in the treatment of liver diseases remains a controversial issue. Therefore, the objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. 525 references were found in the databases, of which 84 papers were retained for closer examination and 36 were deemed suitable for detailed analysis. Silymarin has metabolic and cell-regulating effects at concentrations found in clinical conditions, namely carrier-mediated regulation of cell membrane permeability, inhibition of the 5-lipoxygenase pathway, scavenging of reactive oxygen species (ROS) of the R-OH type and action on DNA-expression, for example, via suppression of nuclear factor (NF)-κB. Pooled data from case record studies involving 452 patients with Amanita phalloides poisoning show a highly significant difference in mortality in favour of silibinin [the main isomer contained in silymarin] (mortality 9.8% vs 18.3% with standard treatment; p < 0.01). The available trials in patients with toxic (e.g. solvents) or iatrogenic (e.g. antispychotic or tacrine) liver diseases, which are mostly outdated and underpowered, do not enable any valid conclusions to be drawn on the value of silymarin. The exception is an improved clinical tolerance of tacrine. In spite of some positive results in patients with acute viral hepatitis, no formally valid conclusion can be drawn regarding the value of silymarin in the treatment of these infections. Although there were no clinical end-points in the four trials considered in patients with alcoholic liver disease, histological findings were reported as improved in two out of two trials, improvement of prothrombin time was significant (two trials pooled) and liver transaminase levels were consistently lower in the silymarin-treated groups. Therefore, silymarin may be of use as an adjuvant in the therapy of alcoholic liver disease. Analysis was performed on five trials with a total of 602 patients with liver cirrhosis. The evidence shows that, compared with placebo, silymarin produces a nonsignificant reduction of total mortality by −4.2% [odds ratio (OR) 0.75 (0.5–1.1)]; but that, on the other hand, the use of silymarin leads to a significant reduction in liver-related mortality of −7% [OR: 0.54 (0.3–0.9); p < 0.01]. An individual trial reported a reduction in the numberof patients with encephalopathy of −8.7% (p = 0.06). In one study of patients with cirrhosis-related diabetes mellitus, the insulin requirement was reduced by −25% (p < 0.01). We conclude that available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the ‘final’ evidence of the efficacy of silymarin.
650 citations
"Preparation and Evaluation of Silym..." refers background in this paper
...It is also reported to be effective in certain cancers.[1-5] The poor aqueous solubility of the drug may lead to dissolution-related bioavailability problems....
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Journal Article•
TL;DR: Silymarin may prove to be a useful drug for hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs, as it is having a good safety profile, better patient tolerability and an effective drug at an affordable price.
Abstract: Silymarin, a flavonolignan from 'milk thistle' (Silybum marianum) plant is used almost exclusively for hepatoprotection and amounts to 180 million US dollars business in Germany alone. In this review we discuss about its safety, efficacy and future uses in liver diseases. The use of silymarin may replace the polyherbal formulations and will avoid the major problems of standardization, quality control and contamination with heavy metals or bacterial toxins. Silymarin consists of four flavonolignan isomers namely--silybin, isosilybin, silydianin and silychristin. Among them, silybin being the most active and commonly used. Silymarin is orally absorbed and is excreted mainly through bile as sulphates and conjugates. Silymarin offers good protection in various toxic models of experimental liver diseases in laboratory animals. It acts by antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, membrane stabilizing, immunomodulatory and liver regenerating mechanisms. Silymarin has clinical applications in alcoholic liver diseases, liver cirrhosis, Amanita mushroom poisoning, viral hepatitis, toxic and drug induced liver diseases and in diabetic patients. Though silymarin does not have antiviral properties against hepatitis virus, it promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation and protects against glutathione depletion. Silymarin may prove to be a useful drug for hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs. The non traditional use of silymarin may make a breakthrough as a new approach to protect other organs in addition to liver. As it is having a good safety profile, better patient tolerability and an effective drug at an affordable price, in near future new derivatives or new combinations of this drug may prove to be useful.
507 citations
"Preparation and Evaluation of Silym..." refers background in this paper
...It is also reported to be effective in certain cancers.[1-5] The poor aqueous solubility of the drug may lead to dissolution-related bioavailability problems....
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Journal Article•
TL;DR: When compared with Silybum, the hepatoprotective effect of Picrorhiza kurroa was found to be similar, or in many cases, superior to the effect of SILYbum.
Abstract: Botanicals have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Basic scientific research has uncovered the mechanisms by which some plants afford their therapeutic effects. Silybum marianum (milk thistle) has been shown to have clinical applications in the treatment of toxic hepatitis, fatty liver, cirrhosis, ischemic injury, radiation toxicity, and viral hepatitis via its antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, immunomodulating, and liver regenerating effects. Picrorhiza kurroa, though less well researched than Silybum, appears to have similar applications and mechanisms of action. When compared with Silybum, the hepatoprotective effect of Picrorhiza was found to be similar, or in many cases, superior to the effect of Silybum.
425 citations
"Preparation and Evaluation of Silym..." refers background in this paper
...It is also reported to be effective in certain cancers.[1-5] The poor aqueous solubility of the drug may lead to dissolution-related bioavailability problems....
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