Skip to main content

Advertisement

SpringerLink
Log in

Formulation of Microemulsion Systems for Dermal Delivery of Silymarin

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

Abstract

Silymarin is a standardized extract from Silybum marianum seeds, known for its many skin benefits such as antioxidant, anti-inflammatory, and immunomodulatory properties. In this study, the potential of several microemulsion formulations for dermal delivery of silymarin was evaluated. The pseudo-ternary phase diagrams were constructed for the various microemulsion formulations which were prepared using glyceryl monooleate, oleic acid, ethyl oleate, or isopropyl myristate as the oily phase; a mixture of Tween 20®, Labrasol®, or Span 20® with HCO-40® (1:1 ratio) as surfactants; and Transcutol® as a cosurfactant. Oil-in-water microemulsions were selected to incorporate 2% w/w silymarin. After six heating–cooling cycles, physical appearances of all microemulsions were unchanged and no drug precipitation occurred. Chemical stability studies showed that microemulsion containing Labrasol® and isopropyl myristate stored at 40°C for 6 months showed the highest silybin remaining among others. The silybin remainings depended on the type of surfactant and were sequenced in the order of: Labrasol® > Tween 20® > Span 20®. In vitro release studies showed prolonged release for microemulsions when compared to silymarin solution. All release profiles showed the best fits with Higuchi kinetics. Non-occlusive in vitro skin permeation studies showed absence of transdermal delivery of silybin. The percentages of silybin in skin extracts were not significantly different among the different formulations (p > 0.05). Nevertheless, some silybin was detected in the receiver fluid when performing occlusive experiments. Microemulsions containing Labrasol® also were found to enhance silymarin solubility. Other drug delivery systems with occlusive effect could be further developed for dermal delivery of silymarin.

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
Fig. 8

Similar content being viewed by others

References

  1. Afaq F, Adhami VM, Ahmad N, Mukhtar H. Botanical antioxidants for chemoprevention of photocarcinogenesis. Front Biosci. 2002;7:784–92.

    Article  Google Scholar 

  2. Křena Vb, Walterováb D. Silybin and silymarin-new effects and applications. Biomed Papers. 2005;149(1):29–41.

    Google Scholar 

  3. Svobodová A, Psotová J, Walterová D. Natural phenolics in the prevention of UV-induced skin damage. A review. Biomed Papers. 2003;147(2):137–45.

    Google Scholar 

  4. Katiyar SK. Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol. 2002;21(6):1213–22.

    PubMed  CAS  Google Scholar 

  5. Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (review). Int J Oncol. 2005;26(1):169–76.

    PubMed  CAS  Google Scholar 

  6. Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forsch Komplementarmed. 2007;14:70–80. doi:10.1159/000100581.

    Article  Google Scholar 

  7. Date AA, Naik B, Nagarsenker MS. Novel drug delivery systems: potential in improving topical delivery of antiacne agents. Skin Pharmacol Physiol. 2006;19(1):2–16. doi:10.1159/000089138.

    Article  PubMed  CAS  Google Scholar 

  8. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev. 2002;54:S77–98. doi:10.1016/s0169-409x(02)00116-3.

    Article  PubMed  CAS  Google Scholar 

  9. Barry BW. Mode of action of penetration enhancers in human skin. J Control Release. 1987;6(1):85–97. doi:10.1016/0168-3659(87)90066-6.

    Article  CAS  Google Scholar 

  10. ICH: validation of analytical procedures: text and methodology Q2(R1). http://www.ich.org/ (1994). Accessed 1 Aug 2009.

  11. Dietary Supplements/Milk Thistle. The United States Pharmacopeia 30 and the National Formulary 25, vol 1. Rockville, MD: The United States Pharmacopeia Convention; 2007. p. 966–7.

    Google Scholar 

  12. Guy RH, Hadgraft J, Kellaway IW, Taylor M. Calculations of drug release rates from particles. Int J Pharm. 1982;11(3):199–207. doi:10.1016/0378-5173(82)90038-2.

    Article  CAS  Google Scholar 

  13. Ho H-O, Hsiao C-C, Sheu M-T. Preparation of microemulsions using polyglycerol fatty acid esters as surfactant for the delivery of protein drugs. J Pharm Sci. 1996;85(2):138–43. doi:10.1021/js950352h.

    Article  PubMed  CAS  Google Scholar 

  14. Mo C, Zhong M, Zhong Q. Investigation of structure and structural transition in microemulsion systems of sodium dodecyl sulfonate + n-heptane + n-butanol + water by cyclic voltammetric and electrical conductivity measurements. J Electroanal Chem. 2000;493(1–2):100–7. doi:10.1016/s0022-0728(00)00350-8.

    CAS  Google Scholar 

  15. Lee J, Lee Y, Kim J, Yoon M, Choi Y. Formulation of microemulsion systems for transdermal delivery of aceclofenac. Arch Pharm Res. 2005;28(9):1097–102. doi:10.1007/bf02977408.

    Article  PubMed  CAS  Google Scholar 

  16. Moulik SP, Paul BK. Structure, dynamics and transport properties of microemulsions. Adv Colloid Interface Sci. 1998;78(2):99–195. doi:10.1016/s0001-8686(98)00063-3.

    Article  CAS  Google Scholar 

  17. Djordjevic L, Primorac M, Stupar M, Krajisnik D. Characterization of caprylocaproyl macrogolglycerides based microemulsion drug delivery vehicles for an amphiphilic drug. Int J Pharm. 2004;271(1–2):11–9. doi:10.1016/j.ijpharm.2003.10.037.

    Article  PubMed  CAS  Google Scholar 

  18. Yuan Y, Li S-m, Mo F-k, Zhong D-f. Investigation of microemulsion system for transdermal delivery of meloxicam. Int J Pharm. 2006;321(1–2):117–23. doi:10.1016/j.ijpharm.2006.06.021.

    Article  PubMed  CAS  Google Scholar 

  19. Junyaprasert VB, Boonme P, Songkro S, Krauel K, Rades T. Transdermal delivery of hydrophobic and hydrophilic local anesthetics from O/W and W/O Brij 97-based microemulsions. J Pharm Pharm Sci. 2007;10(3):288–98.

    PubMed  CAS  Google Scholar 

  20. Bonne C, Sincholle D. Cosmetic preparations useful for opposing skin aging containing an extract of the fruits of Silybum marianum. US patent US 4,749,573, 7 Jun 1988.

  21. Han MH, Yoon WK, Lee H, Han S-B, Lee K, Park S-K, et al. Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice. Int Immunopharmacol. 2007;7(13):1651–8. doi:10.1016/j.intimp.2007.08.019.

    Article  PubMed  CAS  Google Scholar 

  22. Liu L, Pang X, Zhang W, Wang S. Formulation design and in vitro evaluation of silymarin-loaded self-microemulsifying drug delivery systems. Asian J Pharm Sci. 2007;2(4):150–60.

    CAS  Google Scholar 

  23. Woo J, Kim T-S, Park J-H, Chi S-C. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Arch Pharm Res. 2007;30(1):82–9. doi:10.1007/bf02977782.

    Article  PubMed  CAS  Google Scholar 

  24. Špiclin P, Homar M, Zupančič-Valant A, Gašperlin M. Sodium ascorbyl phosphate in topical microemulsions. Int J Pharm. 2003;256(1–2):65–73. doi:10.1016/s0378-5173(03)00063-2.

    Article  PubMed  Google Scholar 

  25. Vicentini FTMC, Simi TRM, Del Ciampo JO, Wolga NO, Pitol DL, Iyomasa MM, et al. Quercetin in w/o microemulsion: In vitro and in vivo skin penetration and efficacy against UVB-induced skin damages evaluated in vivo. Eur J Pharm Biopharm. 2008;69(3):948–57. doi:10.1016/j.ejpb.2008.01.012.

    Article  PubMed  CAS  Google Scholar 

  26. Svobodová A, Zdařilová A, Walterová D, Vostálová J. Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes. J Dermatol Sci. 2007;48(3):213–24. doi:10.1016/j.jdermsci.2007.06.008.

    Article  PubMed  Google Scholar 

  27. Choo S-J, Ryoo I-J, Kim Y-H, Xu G-H, Kim W-G, Kim K-H, et al. Silymarin inhibits melanin synthesis in melanocyte cells. J Pharm Pharmacol. 2009;61(5):663–7. doi:10.1211/jpp.61.05.0016.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Chulalongkorn University Graduate Research Fund for partially financing this study. We also acknowledge Associate Professor Dr. Iman Saad Ahmed, College of Pharmacy, University of Sharjah, United Arab Emirates for her scientific review; Berlin Pharmaceutical Co., Ltd. (Thailand) for supplying silymarin; Croda Co., Ltd. (Thailand) for supplying glyceryl monooleate and ethyl oleate; and Kru Somboon farm (Ratchaburi, Thailand) for supplying the dead newborn pigs.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand

    Vipaporn Panapisal, Sawitree Charoensri & Angkana Tantituvanont

Authors
  1. Vipaporn Panapisal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sawitree Charoensri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angkana Tantituvanont
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vipaporn Panapisal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Panapisal, V., Charoensri, S. & Tantituvanont, A. Formulation of Microemulsion Systems for Dermal Delivery of Silymarin. AAPS PharmSciTech 13, 389–399 (2012). https://doi.org/10.1208/s12249-012-9762-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-012-9762-y

Key words

Search

Navigation