Skip to main content
SpringerLink
Log in

Development of Silymarin Self-Microemulsifying Drug Delivery System with Enhanced Oral Bioavailability

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The objective of this work was to develop a self-microemulsifying drug delivery system (SMEDDS) for improving oral absorption of poorly water-soluble drug, silymarin. The pseudo-ternary phase diagrams were constructed using ethyl linoleate, Cremophor EL, ethyl alcohol, and normal saline to identify the efficient self-microemulsification region. The particle size and its distribution of the resultant microemulsions were determined using dynamic light scattering. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 10% (w/w) of ethyl linoleate, 30% of Cremophor EL, and 60% of ethyl alcohol. The release of silymarin from SMEDDS was significantly faster than that from the commercial silymarin preparation hard capsule (Legalon®). The bioavailability results indicated that the oral absorption of silymarin SMEDDS was enhanced about 2.2-fold compared with the hard capsule in fasted dogs. It could be concluded that SMEDDS would be a promising drug delivery system for poorly water-soluble drugs by the oral route.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

  2. 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 Pharmacokinet. 1990;15:333–8.

    CAS  PubMed  Google Scholar 

  3. Schandalik R, Gatti G, Perucca E. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients. Arzneimittelforschung. 1992;42:964–8.

    CAS  PubMed  Google Scholar 

  4. Chen W, Xia H, Wu W. Optimized preparation of silymarin dripping pills by a central composite design–response surface method. Chin Trad Herb Drug. 2005;36:679–83.

    Google Scholar 

  5. Xiao YY, Song YM, Chen ZP, Ping QN. Preparation of silymarin proliposome: a new way to increase oral bioavailability of silymarin in beagle dogs. Int J Pharm. 2006;319:162–8.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. 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  CAS  PubMed  Google Scholar 

  8. Weyhenmeyer R, Mascher H, Birkmayer J. Study on dose-linearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay. Int J Clin Pharmacol Ther Toxicol. 1992;30:134–8.

    CAS  PubMed  Google Scholar 

  9. Schulz HU, Schurer M, Krumbiegel G, Wachter W, Weyhenmeyer R, Seidel G. The solubility and bioequivalence of silymarin preparations. Arzneimittelforschung. 1995;45:61–4.

    CAS  PubMed  Google Scholar 

  10. Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Deliv Rev. 1997;25:47–58.

    Article  CAS  Google Scholar 

  11. Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm. 1998;167:155–64.

    Article  CAS  Google Scholar 

  12. Kim HJ, Yoon KA, Hahn M, Park ES, Chi SC. Preparation and in vitro evaluation of self-microemulsifying drug delivery systems containing idebenone. Drug Dev Ind Pharm. 2000;26:523–9.

    Article  CAS  PubMed  Google Scholar 

  13. Pouton CW. Lipid formulation for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci. 2000;11:S93–8.

    Article  CAS  PubMed  Google Scholar 

  14. Kommuru TR, Gurley B, Khan MA, Reddy IK. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int J Pharm. 2001;212:233–46.

    Article  CAS  PubMed  Google Scholar 

  15. Itoh K, Matsui S, Tozuka Y, Oguchi T, Yamamoto K. Improvement of physicochemical properties of N-4472 Part II: characterization of N-4472 microemulsion and the enhanced oral absorption. Int J Pharm. 2002;246:75–83.

    Article  CAS  PubMed  Google Scholar 

  16. Holm R, Porter CJH, Edwards GA, Müllertz A, Kristensen HG, Charman WN. Examination of oral absorption and lymphatic transport of halofantrine in triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides. Eur J Pharm Sci. 2003;20:91–7.

    Article  CAS  PubMed  Google Scholar 

  17. Grove M, Müllertz A, Nielsen JL, Pedersen GP. Bioavailability of seocalcitol II: development and characterisation of self-microemulsifying drug delivery systems (SMEDDS) for oral administration containing medium and long chain triglycerides. Eur J Pharm Sci. 2006;28:233–42.

    Article  CAS  PubMed  Google Scholar 

  18. Cirri M, Mura P, Corvi Mora P. Liquid spray formulations of xibornol by using self-microemulsifying drug delivery systems. Int J Pharm. 2007;340:84–91.

    Article  CAS  PubMed  Google Scholar 

  19. Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm. 2004;274:65–73.

    Article  CAS  PubMed  Google Scholar 

  20. Swenson ES, Curatolo WJ. Means to enhance penetration. Adv Drug Deliv Rev. 1992;8:39–42.

    Article  CAS  Google Scholar 

  21. Haus DJ, Mehta SC, Radebaugh GW. Targeting lymphatic transport and modified systemic distribution of CI-976, a lipophilic lipid-regulator drug, via a formulation approach. Int J Pharm. 1994;108:85–93.

    Article  Google Scholar 

  22. Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Deliv Rev. 1997;25:103–28.

    Article  CAS  Google Scholar 

  23. O'Driscoll CM. Lipid-based formulations for intestinal lymphatic delivery. Eur J Pharm Sci. 2002;15:405–15.

    Article  PubMed  Google Scholar 

  24. Liu JB, Xiao YH, Allen C. Polymer-drug compatibility: a guide to the development of delivery systems for the anticancer agent, ellipticine. J Pharm Sci. 2004;93:132–43.

    Article  CAS  PubMed  Google Scholar 

  25. Philipoff W. Micelles and X-rays. J Colloid Sci. 1950;5:169–91.

    Article  Google Scholar 

  26. Riegelman S, Allawala NA, Hrenoff MK, Srait LA. The ultraviolet absorption spectrum as a criterion of the type of solubilization. J Colloid Sci. 1958;13:208–17.

    Article  CAS  Google Scholar 

  27. Folliad KJ, Berke NS. Properties of high-performance concrete containing shrinkage-reducing admixture. Cem Concr Res. 1997;27:1357–64.

    Article  Google Scholar 

  28. Gershanik T, Benita S. Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs. Eur J Pharm Biopharm. 2000;50:179–88.

    Article  CAS  PubMed  Google Scholar 

  29. Yuan Q, Li XR, Wang HJ, Li XY, Liu Y. The absorption kinetics of silymarin microemulsion in rat intestine. Acta Pharm Sin. 2004;39:631–4.

    CAS  Google Scholar 

  30. Charman WN, Stella VJ. Transport of lipophilic molecules by the intestinal lymphatic system. Adv Drug Deliv Rev. 1991;7:1–14.

    Article  CAS  Google Scholar 

  31. Sha XY, Yan GJ, Wu YJ, Li JC, Fang XL. Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells. Eur J Pharm Sci. 2005;24:477–86.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Development of Significant New Drug (New Preparation and New Technology, Grant nos. 2009ZX09310-001) and the National Basic Research Program of China (973 program, no. 2009CB930300).

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China

    Xinru Li, Yanqing Huang, Yanxia Zhou & Yan Liu

  2. Beijing Novartis Pharma Ltd, Beijing, China

    Quan Yuan

Authors
  1. Xinru Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Quan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanqing Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanxia Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, X., Yuan, Q., Huang, Y. et al. Development of Silymarin Self-Microemulsifying Drug Delivery System with Enhanced Oral Bioavailability. AAPS PharmSciTech 11, 672–678 (2010). https://doi.org/10.1208/s12249-010-9432-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-010-9432-x

Key words

Search

Navigation