Solubility increasing experiments of sylimarin with cyclodextrins
Solubility increasing experiments of sylimarin with cyclodextrins
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Title: | Solubility increasing experiments of sylimarin with cyclodextrins |
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Article_Title: | Solubility increasing experiments of sylimarin with cyclodextrins |
Authors: | Ferenc Fenyvesi1, Mátyás Pétervári 1, Lajos Nagy2, Sándor Kéki2, Miklós Zsuga2, Ildikó Bácskay1, Tímea Kiss1, Judit Váradi1, Pálma Fehér1, Zoltán Ujhelyi1, Katalin Réti-Nagy1, Miklós Vecsernyés1* |
Affiliation: | 1Department of Pharmaceutical Technology, University of Debrecen, Debrecen, Hungary 2Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary |
Abstract: | Silymarin formulations with high bioavailability are required for the treatment hepatic disorders. Silymarin, the dry extract of Silybum Marianum is water insoluble and its oral bioavailability is limited. Cyclodextrins are widely used solubility and absorption enhancers therefore we applied the cyclodextrin nano-encapsulation for the improvement of silymarin solubility. Hydroxylpropyl-β-cyclodextrin (HPBCD), randomly methylated β-cyclodextrin (RAMEB), 2,6-di-O-methyl β-cyclodextrin (DIMEB) and Quaternary amino β-cyclodextrin polymer (QABCDP) were used as host molecules. Sylimarin-cyclodextrin complexes were prepared in 1:20 mass ratio and we found that each cyclodextrin was able to increase the water solubility of silymarin. The solutions were stable, thus we can conclude that these cyclodextrins are suitable for the formulations of sylimarin with increased bioavailability. |
Keywords: | silymarin, cyclodextrins, solubility, mass spectrometry, HPLC |
References: | Blumenthal M, Goldberg A, Brinckmann J. Herbal medicine. Expanded commission E monographs: integrative medicine communications; 2000. Carducci R, Armellino MF, Volpe C, Basile G, Caso N, Apicella A, et al. Silibinin and acute poisoning with Amanita phalloides. Minerva Anestesiol 62 (1996) pp. 187-93. Cserháti T, Forgács E. Inclusion complex formation of steroidal drugs with hydroxypropyl-betacyclodextrin studied by charge-transfer chromatography. J Pharm Biomed Anal. 18 (1-2) (1998) pp. 179-85. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 23 (1996) pp. 749–54. D. Voinovich, B. Perissutti, L. Magarotto, D. Ceschia, P. Guiotto, A. Bilia Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers J Pharm Sci, 98 (2009), pp. 215–228 Favari L, Perez-Alvarez V. Comparative effects of colchicines and silymarin on CCl4 chronic liver damage in rats. Arch Med Res 28 (1997) pp. 11-7. Fenyvesi F, Kiss T, Fenyvesi E, Szente L, Veszelka S, Deli MA, Váradi J, Fehér P, Ujhelyi Z, Tósaki A, Vecsernyés M, Bácskay I. Randomly methylated β-cyclodextrin derivatives enhance taxol permeability through human intestinal epithelial Caco-2 cell monolayer. J Pharm Sci. 100(11) (2011) pp. 4734-44. J. He, S. Hou, W. Lu, L. Zhu, J. Feng Preparation, pharmacokinetics and body distribution of silymarin-loaded solid lipid nanoparticles after oral administration J. Biomed. Nanotech. 3 (2007), pp. 195–202 J.S. Woo, T.S. Kim, J.H. Park, S.C. Chi Formulation and biopharmaceutical evaluation of silymarin using SMEDDS Arch. Pharm. Res., 30 (2007), pp. 82–89 Kiss T, Fenyvesi F, Bácskay I, Váradi J, Fenyvesi E, Iványi R, Szente L, Tósaki A, Vecsernyés M. Evaluation of the cytotoxicity of beta-cyclodextrin derivatives: evidence for the role of cholesterol extraction. Eur J Pharm Sci. 40(4) (2010) pp. 376-80 M. Arcari, A. Brambilla, A. Brandt, R. Caponi, G. Corsi, M. Di Rella, F. Solinas, W.P. Wachter A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations Boll. Chim. Farm., 131 (1992), pp. 205–209 Renganathan A. Pharmaco dynamic properties of andrographolide in experimental animals. M.D. thesis. Pharmacology. Pondicherry: Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry University; 1999. Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 61 (2001) pp. 2035-63. S.C. Pradhan & C. Girish Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine Indian J Med Res 124 (2006) pp 491-504 Shamama Javed, PhD; Kanchan Kohli; Mushir Ali Reassessing Bioavailability of Silymarin Altern Med Rev 16(3) (2011) pp. 239-249 Vogel G, Tuchweber B, Trost W. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol 73 (1984) pp. 355-62. W. Chen, H. Xia, W. Wu Optimized preparation of silymarin dripping pills by a central composite design–response surface method Chin. Trad. Herb. Drug, 36 (2005), pp. 679–683 Wachter W, Zaeske H. Process for the manufacture of flavanolignan preparation with improved release and absorbability, compositions obtainable thereby and their use for the preparation of pharmaceuticals. US Patent 6020, 384; 2000. Wang M, Grange LL, Tao J. Hepatoprotective properties of Silybum marianum herbal preparation on ethanolinduced liver damage. Fitoterapia 67 (1996) pp. 167-71. Wellington K, Jarvis B. Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs 15 (2001) pp. 465–89. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 121 (2009), pp.185-193. W. Wei, W. Yang, Q. Li Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system Eur. J. Pharm. Biopharm., 63 (2006), pp. 288–294 X. Yanyu, S. Yunmei, C. Zhipeng, P. Qineng The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats Int. J. Pharm., 307 (2006), pp. 77–82 |
Read_full_article: | pdf/vol14/iss2/JMA14-2-2011-Fenyvesi.pdf |
Correspondence: | Miklós Vecsernyés, University of Debrecen, Debrecen, Faculty of Pharmacy, Department of Pharmaceutical Technology, Egyetem square 1. 4010. Po. Box.: 78. Debrecen, Hungary. +36-30-512-900/22630. E-mail: vecsernyes.miklos@pharm.unideb.hu |
Read full article | |
Article Title: | Solubility increasing experiments of sylimarin with cyclodextrins |
Authors: | Ferenc Fenyvesi1, Mátyás Pétervári 1, Lajos Nagy2, Sándor Kéki2, Miklós Zsuga2, Ildikó Bácskay1, Tímea Kiss1, Judit Váradi1, Pálma Fehér1, Zoltán Ujhelyi1, Katalin Réti-Nagy1, Miklós Vecsernyés1* |
Affiliation: | 1Department of Pharmaceutical Technology, University of Debrecen, Debrecen, Hungary 2Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary |
Abstract: | Silymarin formulations with high bioavailability are required for the treatment hepatic disorders. Silymarin, the dry extract of Silybum Marianum is water insoluble and its oral bioavailability is limited. Cyclodextrins are widely used solubility and absorption enhancers therefore we applied the cyclodextrin nano-encapsulation for the improvement of silymarin solubility. Hydroxylpropyl-β-cyclodextrin (HPBCD), randomly methylated β-cyclodextrin (RAMEB), 2,6-di-O-methyl β-cyclodextrin (DIMEB) and Quaternary amino β-cyclodextrin polymer (QABCDP) were used as host molecules. Sylimarin-cyclodextrin complexes were prepared in 1:20 mass ratio and we found that each cyclodextrin was able to increase the water solubility of silymarin. The solutions were stable, thus we can conclude that these cyclodextrins are suitable for the formulations of sylimarin with increased bioavailability. |
Keywords: | silymarin, cyclodextrins, solubility, mass spectrometry, HPLC |
References: | Blumenthal M, Goldberg A, Brinckmann J. Herbal medicine. Expanded commission E monographs: integrative medicine communications; 2000. Carducci R, Armellino MF, Volpe C, Basile G, Caso N, Apicella A, et al. Silibinin and acute poisoning with Amanita phalloides. Minerva Anestesiol 62 (1996) pp. 187-93. Cserháti T, Forgács E. Inclusion complex formation of steroidal drugs with hydroxypropyl-betacyclodextrin studied by charge-transfer chromatography. J Pharm Biomed Anal. 18 (1-2) (1998) pp. 179-85. Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 23 (1996) pp. 749–54. D. Voinovich, B. Perissutti, L. Magarotto, D. Ceschia, P. Guiotto, A. Bilia Solid state mechanochemical simultaneous activation of the constituents of the Silybum marianum phytocomplex with crosslinked polymers J Pharm Sci, 98 (2009), pp. 215–228 Favari L, Perez-Alvarez V. Comparative effects of colchicines and silymarin on CCl4 chronic liver damage in rats. Arch Med Res 28 (1997) pp. 11-7. Fenyvesi F, Kiss T, Fenyvesi E, Szente L, Veszelka S, Deli MA, Váradi J, Fehér P, Ujhelyi Z, Tósaki A, Vecsernyés M, Bácskay I. Randomly methylated β-cyclodextrin derivatives enhance taxol permeability through human intestinal epithelial Caco-2 cell monolayer. J Pharm Sci. 100(11) (2011) pp. 4734-44. J. He, S. Hou, W. Lu, L. Zhu, J. Feng Preparation, pharmacokinetics and body distribution of silymarin-loaded solid lipid nanoparticles after oral administration J. Biomed. Nanotech. 3 (2007), pp. 195–202 J.S. Woo, T.S. Kim, J.H. Park, S.C. Chi Formulation and biopharmaceutical evaluation of silymarin using SMEDDS Arch. Pharm. Res., 30 (2007), pp. 82–89 Kiss T, Fenyvesi F, Bácskay I, Váradi J, Fenyvesi E, Iványi R, Szente L, Tósaki A, Vecsernyés M. Evaluation of the cytotoxicity of beta-cyclodextrin derivatives: evidence for the role of cholesterol extraction. Eur J Pharm Sci. 40(4) (2010) pp. 376-80 M. Arcari, A. Brambilla, A. Brandt, R. Caponi, G. Corsi, M. Di Rella, F. Solinas, W.P. Wachter A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations Boll. Chim. Farm., 131 (1992), pp. 205–209 Renganathan A. Pharmaco dynamic properties of andrographolide in experimental animals. M.D. thesis. Pharmacology. Pondicherry: Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Pondicherry University; 1999. Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs 61 (2001) pp. 2035-63. S.C. Pradhan & C. Girish Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine Indian J Med Res 124 (2006) pp 491-504 Shamama Javed, PhD; Kanchan Kohli; Mushir Ali Reassessing Bioavailability of Silymarin Altern Med Rev 16(3) (2011) pp. 239-249 Vogel G, Tuchweber B, Trost W. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol 73 (1984) pp. 355-62. W. Chen, H. Xia, W. Wu Optimized preparation of silymarin dripping pills by a central composite design–response surface method Chin. Trad. Herb. Drug, 36 (2005), pp. 679–683 Wachter W, Zaeske H. Process for the manufacture of flavanolignan preparation with improved release and absorbability, compositions obtainable thereby and their use for the preparation of pharmaceuticals. US Patent 6020, 384; 2000. Wang M, Grange LL, Tao J. Hepatoprotective properties of Silybum marianum herbal preparation on ethanolinduced liver damage. Fitoterapia 67 (1996) pp. 167-71. Wellington K, Jarvis B. Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs 15 (2001) pp. 465–89. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 121 (2009), pp.185-193. W. Wei, W. Yang, Q. Li Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system Eur. J. Pharm. Biopharm., 63 (2006), pp. 288–294 X. Yanyu, S. Yunmei, C. Zhipeng, P. Qineng The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats Int. J. Pharm., 307 (2006), pp. 77–82 |
*Correspondence: | Miklós Vecsernyés, University of Debrecen, Debrecen, Faculty of Pharmacy, Department of Pharmaceutical Technology, Egyetem square 1. 4010. Po. Box.: 78. Debrecen, Hungary. +36-30-512-900/22630. E-mail: vecsernyes.miklos@pharm.unideb.hu |