Abstract
This study aimed to investigate the performance of the eutectic mixture of menthol and camphor (1:1, w/w) in nanoemulsion formulation for enhanced transdermal penetration of water-insoluble glabridin. Glabridin solubility in different media was determined by a shaking bottle method. The pseudoternary phase diagrams of the oil phase (drug-loaded eutectic mixture or IPM), the surfactant (Tween 80:glycerol = 2:1, w/w), and water were constructed using the aqueous titration method. The obtained glabridin nanoemulsions were characterized and compared on their particle sizes, in vitro and in vivo penetration performance on rat skin, and storage stability. The nanoemulsion formulation was optimized as 0.25% glabridin, 5% oil phase, 10% Tween 80, 5% glycerol, and 79.75% water. The obtained nanoemulsions showed a mean droplet size of nearly 100 nm for different oil phases. And the stability of both formulations was similar after storage for 3 months. In vitro skin permeation study showed that the nanoemulsion formulation with eutectic mixture exhibited higher skin permeability (28.26 μg/cm2) than that with IPM (9.94 μg/cm2) or the drug solution formulation (3.82 μg/cm2), which was further confirmed by in vivo skin permeation tests on the rat skin and human skin. The eutectic mixture is a preferable solvent for glabridin, and its nanoemulsion can be used as an excellent nanocarrier for enhanced transdermal delivery of glabridin.
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References
Wiedersberg S, Guy RH. Transdermal drug delivery: 30+ years of war and still fighting! J Control Release. 2014;190:150–6. doi:10.1016/j.jconrel.2014.05.022.
Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21. doi:10.1016/j.ijpharm.2013.02.040.
Mohammed D, Hirata K, Hadgraft J, Lane ME. Influence of skin penetration enhancers on skin barrier function and skin protease activity. Eur J Pharm Sci. 2014;51:118–22. doi:10.1016/j.ejps.2013.09.009.
Akbari J, Saeedi M, Farzin D, Morteza-Semnani K, Esmaili Z. Transdermal absorption enhancing effect of the essential oil of Rosmarinus officinalis on percutaneousabsorption of Na diclofenac from topical gel. Pharm Biol. 2015;53(10):1442–7. doi:10.3109/13880209.2014.984855.
Krishnaiah YS, Satyanarayana V, Karthikeyan RS. Penetration enhancing effect of menthol on the percutaneous flux of nicardipine hydrochloride through excised rat epidermis from hydroxypropyl cellulose gels. Pharm Dev Technol. 2002;7(3):305–15. doi:10.1081/PDT-120005727.
Lan Y, Wang J, Li H, Zhang Y, Chen Y, Zhao B, et al. Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids. Pharm Dev Technol. 2016;21(4):389–98. doi:10.3109/10837450.2015.1011660.
Patel T, Ishiuji Y, Yosipovitch G. Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol. 2007;57(5):873–8. doi:10.1016/j.jaad.2007.04.008.
Chen W, Vermaak I, Viljoen A. Camphor-a fumigant during the Black Death and a coveted fragrant wood in ancient Egypt and Babylon—a review. Molecules. 2013;18(5):5434–54. doi:10.3390/molecules18055434.
Gohel MC, Nagori SA. Fabrication and design of transdermal fluconazole spray. Pharm Dev Technol. 2009;14(2):208–15. doi:10.1080/10837450802498936.
Martin D, Valdez J, Boren J, Mayersohn M. Dermal absorption of camphor, menthol, and methyl salicylate in humans. J Clin Pharmacol. 2004;44(10):1151–7. doi:10.1177/0091270004268409.
Gohel MC, Nagori SA. Fabrication and evaluation of hydrogel thickened microemulsion of ibuprofen for topical delivery. Indian J Pharm Educ Res. 2010;44:189–96.
Nohynek GJ, Dufour EK. Nano-sized cosmetic formulations or solid nanoparticles in sunscreens: a risk to human health? Arch Toxicol. 2012;86(7):1063–75. doi:10.1007/s00204-012-0831-5.
Santos P, Watkinson AC, Hadgraft J, Lane ME. Influence of penetration enhancer on drug permeation from volatile formulations. Int J Pharm. 2012;439(1–2):260–8. doi:10.1016/j.ijpharm.2012.09.031.
Tuntarawongsa S, Phaechamud T. Menthol, borneol, camphor and WS-3 eutectic mixture. Adv Mater Res. 2012;506:355–8. doi:10.4028/www.scientific.net/AMR.506.355.
Shanker K, Fatima A, Negi AS, Gupta VK, Darokar MP, Gupta MM, et al. RP-HPLC method for the quantitation of glabridin in Yashti-madhu (Glycyrrhiza glabra). Chromatographia. 2007;65(11–12):771–4.
Chen J, Shen Q, Luo M. Transdermal delivery of paeonol using cubic gel and microemulsion gel. Int J Nanomedicine. 2011;6:1603–10. doi:10.2147/IJN.S22667.
Baek JS, Lim JH, Kang JS, Shin SC, Jung SH, Cho CW. Enhanced transdermal drug delivery of zaltoprofen using a novel formulation. Int J Pharm. 2013;453(2):358–62. doi:10.1016/j.ijpharm.2013.05.059.
Tiossi RF, Da Costa JC, Miranda MA, Praça FS, McChesney JD, Bentley MV, et al. In vitro and in vivo evaluation of the delivery of topical formulations containing glycoalkaloids of Solanum lycocarpum fruits. Eur J Pharm Biopharm. 2014;88(1):28–33. doi:10.1016/j.ejpb.2014.01.010.
Sintov AC, Greenberg I. Comparative percutaneous permeation study using caffeine-loaded microemulsion showing low reliability of the frozen/thawed skin models. Int J Pharm. 2014;471(1–2):516–24. doi:10.1016/j.ijpharm.2014.05.040.
Sintov AC. Transdermal delivery of curcumin via microemulsion. Int J Pharm. 2015;481(1–2):97–103. doi:10.1016/j.ijpharm.2015.02.005.
Gala U, Chuong MC, Varanasi R, Chauhan H. Characterization and comparison of lidocaine-tetracaine and lidocaine-camphor eutectic mixtures based on their crystallization and hydrogen-bonding abilities. AAPS Pharm SciTech. 2015;16(3):528–36. doi:10.1208/s12249-014-0242-4.
Takeuchi H, Mano Y, Terasaka S, Sakurai T, Furuya A, Urano H, Sugibayashi K. Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study. Exp Anim. 2011;60(4):373–84.
Ao M, Shi Y, Cui Y, Guo W, Wang J, Yu L. Factors influencing glabridin stability. Nat Prod Commun. 2010;5(12):1907–12.
Shakeel F, Shafiq S, Haq N, Alanazi FK, Alsarra IA. Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview. Expert Opin Drug Deliv. 2012;9(8):953–74. doi:10.1517/17425247.2012.696605.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (81360644) and the Natural Science Foundation of Ningxia (NZ15145).
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The experiments comply with the current laws of the country in which they were performed. All procedures were approved by the Research Ethics Committee, General Hospital of Ningxia Medical University.
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The authors declare that they have no conflict of interest.
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Chen Liu and Jin Hu contributed equally to this work and should be considered co-first authors
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Liu, C., Hu, J., Sui, H. et al. Enhanced skin permeation of glabridin using eutectic mixture-based nanoemulsion. Drug Deliv. and Transl. Res. 7, 325–332 (2017). https://doi.org/10.1007/s13346-017-0359-6
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DOI: https://doi.org/10.1007/s13346-017-0359-6