Skip to main content

Advertisement

SpringerLink
Log in

A Novel Apremilast Nail Lacquer Formulation for the Treatment of Nail Psoriasis

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

Abstract

The objective was to prepare a novel nail lacquer formulation to improve the ungual and trans-ungual delivery of apremilast for the potential treatment of nail psoriasis. Nail lacquer formulation was prepared using Eudragit® S 100 as a film-forming polymer and the mixture of ethanol, ethyl acetate, and water as a solvent system. As a result of high-throughput screening studies, dexpanthenol and salicylic acid were found to be the potential penetration enhancers. After 7 days of in vitro studies, the cumulative amount of apremilast delivered by the nail lacquer formulation across the nail plate was found to be ~3-fold (0.52 ± 0.07 μg/cm2) more compared to control (nail lacquer formulation without enhancers) (0.19 ± 0.02 μg/cm2). The cumulative amount of apremilast retained in the nail plate in the case of nail lacquer formulation was 1.26 ± 0.18 μg/mg which was found to be ~2-fold more compared to control (0.57 ± 0.07 μg/mg). Human subject studies were performed on the nails of thumb and index finger of six volunteers for 15 days. As a result, the cumulative amount of apremilast retained in the free distal edge of the nail plate in the case of nail lacquer was found to be ~2-fold (0.93 ± 0.14 μg/mg) more related to control (0.41 ± 0.04 μg/mg). As a conclusion, nail lacquer formulation was found to be capable of delivering a substantial amount of apremilast into the nail apparatus; thus, it can be a potential option for the treatment of nail psoriasis.

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
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

Abbreviations

Kolliphor® CS 20:

Polyoxyl 20 Cetostearyl Ether

Kolliphor™ HS 15:

Polyoxyl 15 hydroxystearate

Kolliphor™ RH 40:

Polyoxyl 40 hydrogenated castor oil

Vitamin E TPGS:

Vitamin E polyethylene glycol succinate

PEG 400:

Polyethylene glycol 400

Kolliphor® EL:

Polyoxyl 35 castor oil

HPMC:

Hydroxypropyl methyl cellulose

Eudragit® S 100:

Methacrylic Acid - Methyl Methacrylate Copolymer (1:2)

References

  1. Sanchez Regana M, Marquez Balbas G, Umbert Millet P. Nail psoriasis: a combined treatment with 8% clobetasol nail lacquer and tacalcitol ointment. J Eur Acad Dermatol Venereol. 2008;22:963–9.

    Article  CAS  PubMed  Google Scholar 

  2. Manhart R, Rich P. Nail psoriasis. Clin Exp Rheumatol. 2015;33:S7–13.

    PubMed  Google Scholar 

  3. Silva MF, Fortes MR, Miot LD, Marques SA. Psoriasis: correlation between severity index (PASI) and quality of life index (DLQI) in patients assessed before and after systemic treatment. An Bras Dermatol. 2013;88:760–3.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Papp K, Cather JC, Rosoph L, Sofen H, Langley RG, Matheson RT, Hu C, Day RM. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet. 2012;380:738–46.

    Article  CAS  PubMed  Google Scholar 

  5. Oram Y, Akkaya AD. Treatment of nail psoriasis: common concepts and new trends. Dermatol Res Pract. 2013;2013:180496.

    PubMed  PubMed Central  Google Scholar 

  6. Edwards F, de Berker D. Nail psoriasis: clinical presentation and best practice recommendations. Drugs. 2009;69:2351–61.

    Article  CAS  PubMed  Google Scholar 

  7. McCann FE, Palfreeman AC, Andrews M, Perocheau DP, Inglis JJ, Schafer P, Feldmann M, Williams RO, Brennan FM. Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res Ther. 2010;12:R107.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Crowley JJ, Weinberg JM, Wu JJ, Robertson AD, Van Voorhees AS, National Psoriasis F. Treatment of nail psoriasis: best practice recommendations from the Medical Board of the National Psoriasis Foundation. JAMA Dermatol. 2015;151:87–94.

    Article  PubMed  Google Scholar 

  9. Pasch MC. Nail psoriasis: a review of treatment options. Drugs. 2016;76:675–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kumar N, Goldminz AM, Kim N, Gottlieb AB. Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med. 2013;11:96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kushwaha A, Murthy RN, Murthy SN, Elkeeb R, Hui X, Maibach HI. Emerging therapies for the treatment of ungual onychomycosis. Drug Dev Ind Pharm. 2015;41:1575–81.

    Article  CAS  PubMed  Google Scholar 

  12. Kushwaha A, Jacob M, Shiva Kumar HN, Hiremath S, Aradhya S, Repka MA, Murthy SN. Trans-ungual delivery of itraconazole hydrochloride by iontophoresis. Drug Dev Ind Pharm. 2015;41:1089–94.

    Article  CAS  PubMed  Google Scholar 

  13. Kushwaha A, Shivakumar HN, Murthy SN. Iontophoresis for drug delivery into the nail apparatus: exploring hyponychium as the site of delivery. Drug Dev Ind Pharm. 2016;42:1678–82.

    Article  CAS  PubMed  Google Scholar 

  14. Nair AB, Chakraborty B, Murthy SN. Effect of polyethylene glycols on the trans-ungual delivery of terbinafine. Curr Drug Deliv. 2010;7:407–14.

    Article  CAS  PubMed  Google Scholar 

  15. Nair AB, Kim HD, Chakraborty B, Singh J, Zaman M, Gupta A, Friden PM, Murthy SN. Ungual and trans-ungual iontophoretic delivery of terbinafine for the treatment of onychomycosis. J Pharm Sci. 2009;98:4130–40.

    Article  CAS  PubMed  Google Scholar 

  16. Nair AB, Sammeta SM, Kim HD, Chakraborty B, Friden PM, Murthy SN. Alteration of the diffusional barrier property of the nail leads to greater terbinafine drug loading and permeation. Int J Pharm. 2009;375:22–7.

    Article  CAS  PubMed  Google Scholar 

  17. Nair AB, Vaka SR, Sammeta SM, Kim HD, Friden PM, Chakraborty B, Murthy SN. Trans-ungual iontophoretic delivery of terbinafine. J Pharm Sci. 2009;98:1788–96.

    Article  CAS  PubMed  Google Scholar 

  18. Murthy SN, Vaka SR, Sammeta SM, Nair AB. TranScreen-N: method for rapid screening of trans-ungual drug delivery enhancers. J Pharm Sci. 2009;98:4264–71.

    Article  CAS  PubMed  Google Scholar 

  19. Apremilast High performance liquid chromatography. ApexBio Tech LLC. http://www.apexbt.com/downloader/document/A4317/HPLC.pdf. Accessed 20 Feb 2015.

  20. Kushwaha AS, Sharma P, Shivakumar HN, Rappleye C, Zukiwski A, Proniuk S, Murthy SN. Trans-ungual Delivery of AR-12, a novel antifungal drug. AAPS PharmSciTech 2017.

  21. Guidance for Industry Stability Testing of Drug Substances and Drug Products Food and Drug Administration 1998. https://www.fda.gov/ohrms/dockets/98fr/980362gd.pdf. Accessed 5 Mar 2015.

  22. Shivakumar HN, Vaka SR, Madhav NV, Chandra H, Murthy SN. Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosis. J Pharm Sci. 2010;99:4267–76.

    Article  CAS  PubMed  Google Scholar 

  23. Murthy SN, Waddell DC, Shivakumar HN, Balaji A, Bowers CP. Iontophoretic permselective property of human nail. J Dermatol Sci. 2007;46:150–2.

    Article  CAS  PubMed  Google Scholar 

  24. Nair AB, Kim HD, Davis SP, Etheredge R, Barsness M, Friden PM, Murthy SN. An ex vivo toe model used to assess applicators for the iontophoretic ungual delivery of terbinafine. Pharm Res. 2009;26:2194–201.

    Article  CAS  PubMed  Google Scholar 

  25. Manda P, Kushwaha AS, Kundu S, Shivakumar HN, Jo SB, Murthy SN. Delivery of ziconotide to cerebrospinal fluid via intranasal pathway for the treatment of chronic pain. J Control Release. 2016;224:69–76.

    Article  CAS  PubMed  Google Scholar 

  26. Murdan S, Hinsu D, Guimier M. A few aspects of transonychial water loss (TOWL): inter-individual, and intra-individual inter-finger, inter-hand and inter-day variabilities, and the influence of nail plate hydration, filing and varnish. Eur J Pharm Biopharm. 2008;70:684–9.

    Article  CAS  PubMed  Google Scholar 

  27. Gunt HB, Kasting GB. Effect of hydration on the permeation of ketoconazole through human nail plate in vitro. Eur J Pharm Sci. 2007;32:254–60.

    Article  CAS  PubMed  Google Scholar 

  28. Marty J-PL. Amorolfine nail lacquer: a novel formulation. J Eur Acad Dermatol Venereol. 1995;4:S17–21.

    Article  Google Scholar 

  29. Quintanar-Guerrero D, Ganem-Quintanar A, Tapia-Olguin P, Kalia YN, Buri P. The effect of keratolytic agents on the permeability of three imidazole antimycotic drugs through the human nail. Drug Dev Ind Pharm. 1998;24:685–90.

    Article  CAS  PubMed  Google Scholar 

  30. Kyowa. D-Panthenol/Dexpanthenol. https://www.in-cosmetics.com/__novadocuments/2622. Accessed 3 Mar 2015.

  31. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E: critical review of its current use in cosmetic and clinical dermatology. Dermatol Surg. 2005;31:805–13.

    Article  CAS  PubMed  Google Scholar 

  32. Guo Y, Luo J, Tan S, Otieno BO, Zhang Z. The applications of vitamin E TPGS in drug delivery. Eur J Pharm Sci. 2013;49:175–86.

    Article  CAS  PubMed  Google Scholar 

  33. Seljak KB, Berginc K, Trontelj J, Zvonar A, Kristl A, Gašperlin M. A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and Presystemic metabolism. J Pharm Sci. 2014;103:3491–500.

    Article  CAS  PubMed  Google Scholar 

  34. Thong H-Y, Zhai H, Maibach HI. Percutaneous penetration enhancers: an overview. Skin Pharmacol Physiol. 2007;20:272–82.

    Article  PubMed  Google Scholar 

  35. Guideline IHT. Guidance for Industry Q1A (R2) Stability testing of new drug substances andproducts. 2003. https://www.fda.gov/downloads/drugs/guidances/ucm073369.pdf. Accessed 3 Mar 2015.

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, The University of Mississippi, University, MS, 38677, USA

    Avadhesh Singh Kushwaha, Michael A. Repka & S. Narasimha Murthy

Authors
  1. Avadhesh Singh Kushwaha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Repka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Narasimha Murthy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Narasimha Murthy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kushwaha, A.S., Repka, M.A. & Narasimha Murthy, S. A Novel Apremilast Nail Lacquer Formulation for the Treatment of Nail Psoriasis. AAPS PharmSciTech 18, 2949–2956 (2017). https://doi.org/10.1208/s12249-017-0776-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-017-0776-3

Key words

Search

Navigation