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Silymarin Glyceryl Monooleate/Poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability

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  • Theme: Advanced Technologies for Oral Controlled Release
  • Published:
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Abstract

Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

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References

  1. Kvasnicka F, Biba B, Sevcik R, Voldrich M, Krátká J. Analysis of the active components of silymarin. J Chromatogr A. 2003;990:239–45.

    Article  PubMed  CAS  Google Scholar 

  2. Quaglia MG, Bossù E, Donati E, Mazzanti G, Brandt A. Determination of silymarin in the extract from the dried silybum marianum fruits by high performance liquid chromatography and capillary electrophoresis. J Pharm Biomed Anal. 1999;19:435–42.

    Article  PubMed  CAS  Google Scholar 

  3. Škottová N, Krecman V, Simánek V. Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro. Phytother Res. 1999;13:535–7.

    Article  PubMed  Google Scholar 

  4. Lu C, Lu Y, Chen J, Zhang WT, Wu W. Synchronized and sustained release of multiple components in silymarin from erodible glyceryl monostearate matrix system. Eur J Pharm Biopharm. 2007;66:210–9.

    Article  PubMed  CAS  Google Scholar 

  5. Basaga H, Poli G, Tekkaya C, Aras I. Free radical scavenging and antioxidative properties of “silibin” complexs on microsomal lipid peroxidation. Cell Biochem Funct. 1997;15:27–33.

    Article  PubMed  CAS  Google Scholar 

  6. Morazzoni P, Bombardelli E. Silybum marianum (Carduus marianus). Fitoterapia. 1995;66:3–42.

    CAS  Google Scholar 

  7. Pepping J. Milk thistle: Silybum marianum. Am J Health Syst Pharm. 1999;56:1195–7.

    PubMed  CAS  Google Scholar 

  8. Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on IdB 1016, a silybin-phosphatidylcholine complex, in healthy human subjects. Eur J Drug Metab Pharm. 1990;15:333–8.

    Article  CAS  Google Scholar 

  9. Sun N, Wei X, Wu B, Chen J, Lu Y, Wu W. Enhanced dissolution of silymarin/polyvinylpyrrolidone solid dispersion pellets prepared by a one-step fluid-bed coating technique. Powd Technol. 2008;182:72–80.

    Article  CAS  Google Scholar 

  10. Filburn CR, Kettenacker R, Griffin DW. Bioavailability of a silybin–phosphatidylcholine complex in dogs. J Vet Pharmacol Ther. 2007;30:132–8.

    Article  PubMed  CAS  Google Scholar 

  11. Wu W, Wang Y, Que L. Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur J Pharm Biopharm. 2006;63:288–94.

    Article  PubMed  CAS  Google Scholar 

  12. Woo JS, Kim TS, Park JH, Chi SC. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Arch Pharm Res. 2007;30:82–9.

    Article  PubMed  CAS  Google Scholar 

  13. Sun N, Zhang X, Lu Y, Wu W. In vitro evaluation and pharmacokinetics in dogs of solid dispersion pellets containing Silybum marianum extract prepared by fluid-bed coating. Plant Med. 2008;74:126–32.

    Article  CAS  Google Scholar 

  14. Harris RZ, Jang GR, Tsunoda S. Dietary effects on drug metabolism and transport. Clin Pharmacokinet. 2003;42:1071–88.

    Article  PubMed  CAS  Google Scholar 

  15. Singh BN. Effects of food on clinical pharmacokinetics. Clin Pharmacokinet. 1999;37:213–55.

    Article  PubMed  CAS  Google Scholar 

  16. Thomson AB, Schoeller C, Keelan M, Smith L, Clandinin MT. Lipid absorption: passing through the unstirred layers, brush-border membrane, and beyond. Can J Physiol Pharmacol. 1993;71:531–55.

    Article  PubMed  CAS  Google Scholar 

  17. Porter CJ, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6:231–48.

    Article  PubMed  CAS  Google Scholar 

  18. Lai J, Chen JM, Lu Y, Sun J, Hu FQ, Yin ZN, et al. Glyceryl monooleate/poloxamer 407 cubic nanoparticles as oral drug delivery systems: I. In vitro evaluation and enhanced oral bioavailability of the poorly water-soluble drug simvastatin. AAPS PharmSciTech. 2009;10:960–6.

    Article  PubMed  CAS  Google Scholar 

  19. Lai J, Lu Y, Yin Z, Hu F, Wu W. Pharmacokinetics and enhanced oral bioavailability in beagle dogs of cyclosporine A encapsulated in glyceryl monooleate/poloxamer 407 cubic nanoparticles. Int J Nanomedicine. 2010;5:13–23.

    PubMed  CAS  Google Scholar 

  20. Boyd BJ, Whittaker DV, Khoo SM, Davey G. Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int J Pharm. 2006;309:218–26.

    Article  PubMed  CAS  Google Scholar 

  21. Boyd BJ, Khoo SM, Whittaker DV, Davey G, Porter CJ. A lipid-based liquid crystalline matrix that provides sustained release and enhanced oral bioavailability for a model poorly water soluble drug in rats. Int J Pharm. 2007;340:52–60.

    Article  PubMed  CAS  Google Scholar 

  22. Nguyen TH, Hanley T, Porter CJ, Larson I, Boyd BJ. Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water-soluble drugs II. In-vivo evaluation. J Pharm Pharmacol. 2010;62:856–65.

    PubMed  CAS  Google Scholar 

  23. Shah MH, Paradkar A. Cubic liquid crystalline glyceryl monooleate matrices for oral delivery of enzyme. Int J Pharm. 2005;294:161–71.

    Article  PubMed  CAS  Google Scholar 

  24. Spicer PT, Small WB, Lynch ML, Burns JL. Dry powder precursors of cubic liquid crystalline nanoparticles (cubosomes). J Nanopart Res. 2002;4:297–311.

    Article  CAS  Google Scholar 

  25. Sek L, Porter CJ, Charman WN. Characterisation and quantification of medium chain and long chain triglycerides and their in vitro digestion products, by HPTLC coupled with in situ densitometric analysis. J Pharm Biomed Anal. 2001;25:651–61.

    Article  PubMed  CAS  Google Scholar 

  26. Han SF, Yao TT, Zhang XX, Gan L, Zhu C, Yu HZ, et al. Lipid-based formulations to enhance oral bioavailability of the poorly water-soluble drug anethol trithione: effects of lipid composition and formulation. Int J Pharm. 2009;379:18–24.

    Article  PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

This work was partly supported by grants from the Ministry of Education of China (200802461092), the National Key Basic Research Program of China (2009CB930300, 2007CB935800), and Shanghai Municipal Commission of Education (10SG05).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Ruyue Lian, Yi Lu, Jianping Qi, Yanan Tan, Mengmeng Niu, Peipei Guan & Wei Wu

  2. Department of Pharmaceutics, School of Pharmacy, Zhejiang University, Hangzhou, 310058, China

    Fuqiang Hu

Authors
  1. Ruyue Lian
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  2. Yi Lu
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  3. Jianping Qi
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  4. Yanan Tan
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  7. Fuqiang Hu
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  8. Wei Wu
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Correspondence to Wei Wu.

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Guest Editors: Michael Repka, Joseph Reo, Linda Felton, and Stephen Howard

Ruyue Lian and Yi Lu contributed equally to this article.

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Lian, R., Lu, Y., Qi, J. et al. Silymarin Glyceryl Monooleate/Poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability. AAPS PharmSciTech 12, 1234–1240 (2011). https://doi.org/10.1208/s12249-011-9666-2

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  • DOI: https://doi.org/10.1208/s12249-011-9666-2

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