Skip to main content

Advertisement

SpringerLink
Log in

Nanocarrier for the Transdermal Delivery of an Antiparkinsonian Drug

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

Abstract

The purpose of the present study was to investigate the potential of nanoemulsions as nanodrug carrier systems for the percutaneous delivery of ropinirole. Nanoemulsions comprised Capryol 90 as the oil phase, Tween 20 as the surfactant, Carbitol as the cosurfactant, and water as an external phase. The effects of composition of nanoemulsion, including the ratio of surfactant and cosurfactant (S mix) and their concentration on skin permeation, were evaluated. All the prepared nanoemulsions showed a significant increase in permeation parameters such as steady state flux (J ss) and permeability coefficient (K p) when compared to the control (p < 0.01). Nanoemulsion composition (NEL3) comprising ropinirole (0.5% w/w), Capryol 90 (5% w/w), S mix 2:1 (35% w/w), and water (59.5% w/w) showed the highest flux (51.81 ± 5.03 µg/cm2/h) and was selected for formulation into nanoemulsion gel. The gel was further optimized with respect to oil concentration (Capryol 90), polymer concentration (Carbopol), and drug content by employing the Box–Behnken design, which statistically evaluated the effects of these components on ropinirole permeation. Oil and polymer concentrations were found to have a negative influence on permeation, while the drug content had a positive effect. Nanoemulsion gel showed a 7.5-fold increase in skin permeation rate when compared to the conventional hydrogel. In conclusion, the results of the present investigation suggested a promising role of nanoemulsions in enhancing the transdermal permeation of ropinirole.

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

Similar content being viewed by others

References

  1. Hely MA, Morris Reid WGJ. Sydney multicenter study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20:190–9.

    Article  PubMed  Google Scholar 

  2. Schrag A, Jahanshahi M, Quinn NP. What contributes to quality of life in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2000;69:308–12.

    Article  CAS  PubMed  Google Scholar 

  3. Global Parkinson’s disease Survey Steering Committee. Factors impacting on quality of life in Parkinson’s disease: results from an international survey. Mov Disord. 2002;17:60–7.

    Article  Google Scholar 

  4. Findley L, Aujla M, Bain PG, Baker M, Beech C, Bowman C, et al. Direct economic impact of Parkinson’s disease: a research survey in the United Kingdom. Mov Disord. 2003;18:1139–45.

    Article  PubMed  Google Scholar 

  5. Brandabur MM. Current therapy in Parkinson’s disease. Surg Neurol. 1999;52:318–22.

    Article  CAS  PubMed  Google Scholar 

  6. Ball J. Current advances in Parkinson’s disease. Trends Neurosci. 2001;24:367–9.

    Article  CAS  PubMed  Google Scholar 

  7. Golbe LI. Young-onset Parkinson’s disease: a clinical review. Neurology. 1991;41:168–73.

    CAS  PubMed  Google Scholar 

  8. Rinne UK. Treatment of early Parkinson disease. Parkinsonism Relat Disord. 2001;7:59–62.

    Article  Google Scholar 

  9. Kaye CM, Nicholls B. Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet. 2000;39:243–54.

    Article  CAS  PubMed  Google Scholar 

  10. Standaert DG, Young AB. In: Bruton LL, Lazo JS, Parker KL, editors. Goodman Gilman’s the pharmacological basis of therapeutics, 11th edn. International Edition. New York: McGraw-Hill; 2006. p. 527–538.

  11. Matheson AJ, Spencer CM. Ropinirole: a review of its use in the management of Parkinson’s disease. Drugs. 2000;60:115–37.

    Article  CAS  PubMed  Google Scholar 

  12. Dollery C (ed). Therapeutic drugs. 2nd ed., vol. 2. Edinburgh: Churchill Livingstone; 1999. p. R50–R54.

  13. Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonucelli U, Damier P, et al. Levodopa in the treatment of Parkinson's disease: current controversies. Mov Disord. 2004;19:97–1005.

    Article  Google Scholar 

  14. Walters KA. Penetration enhancers and their use in transdermal therapeutic systems. In: Hadgraft J, Guy RH, editors. Transdermal drug delivery, development issues and research initiatives. New York: Marcel Dekker; 1989. p. 197–246.

    Google Scholar 

  15. Kim BS, Won M, Lee KM, Kim S. In vitro permeation studies of nanoemulsions containing ketoprofen as a model drug. Drug Del. 2008;15:465–9.

    Article  CAS  Google Scholar 

  16. Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Design and development of oral oil in water ramipril nanoemulsion formulation: in vitro and in vivo assessment. J Biomed Nanotech. 2007;3:1–17.

    Article  Google Scholar 

  17. Azeem A, Khan ZI, Aqil M, Ahmad FJ, Khar RK, Talegaonkar S. Microemulsions as a surrogate carrier for dermal drug delivery. Drug Dev Ind Pharm. 2009;35:525–47.

    Article  CAS  PubMed  Google Scholar 

  18. Azeem A, Rizwan M, Ahmad FJ, Khan ZI, Khar RK, Aqil M, et al. Emerging role of microemulsions in cosmetics. Recent Pat Drug Deliv Formul. 2008;2:275–89.

    Article  CAS  PubMed  Google Scholar 

  19. Heuschkel S, Goebel A, Neubert RHH. Microemulsions—modern colloidal carrier for dermal and transdermal drug delivery. J Pharm Sci. 2008;97:603–31.

    Article  CAS  PubMed  Google Scholar 

  20. El Maghraby GM. Transdermal delivery of hydrocortisone from eucalyptus oil microemulsion: effects of cosurfactants. Int J Pharm. 2008;355:285–92.

    Article  CAS  PubMed  Google Scholar 

  21. Shevachman M, Garti N, Shani A, Sintov AC. Enhanced percutaneous permeability of diclofenac using a new U-type dilutable microemulsion. Drug Dev Ind Pharm. 2008;34:403–12.

    Article  CAS  PubMed  Google Scholar 

  22. Huang YB, Lin YH, Lu TM, Wang RJ, Tsai YH, Wu PC. Transdermal delivery of capsaicin derivative-sodium nonivamide acetate using microemulsions as vehicles. Int J Pharm. 2008;349:206–11.

    Article  CAS  PubMed  Google Scholar 

  23. Yuan JS, Ansari M, Samaan M, Acosta EJ. Linker-based lecithin microemulsions for transdermal delivery of lidocaine. Int J Pharm. 2008;349:130–43.

    Article  CAS  PubMed  Google Scholar 

  24. Biruss B, Kählig H, Valenta C. Evaluation of an eucalyptus oil containing topical drug delivery system for selected steroid hormones. Int J Pharm. 2007;328:142–51.

    Article  CAS  PubMed  Google Scholar 

  25. Biruss B, Valenta C. The advantage of polymer addition to a non-ionic oil in water microemulsion for the dermal delivery of progesterone. Int J Pharm. 2008;349:269–73.

    Article  CAS  PubMed  Google Scholar 

  26. Kamal MA, Iimura N, Nabekura T, Kitagawa S. Enhanced skin permeation of diclofenac by ion-pair formation and further enhancement by microemulsion. Chem Pharm Bull. 2007;55:368–71.

    Article  CAS  PubMed  Google Scholar 

  27. Kantarci G, Ozgüney I, Karasulu HY, Arzi S, Güneri T. Comparison of different water/oil microemulsions containing diclofenac sodium: preparation, characterization, release rate, and skin irritation studies. AAPS Pharm Sci Tech. 2007;8:E91.

    Article  Google Scholar 

  28. Yuan Y, Li SM, Mo FK, Zhong DF. Investigation of microemulsion system for transdermal delivery of meloxicam. Int J Pharm. 2006;321:117–23.

    Article  CAS  PubMed  Google Scholar 

  29. Lee PJ, Langer R, Shastri VP. Novel microemulsion enhancer formulation for simultaneous transdermal delivery of hydrophilic and hydrophobic drugs. Pharm Res. 2003;20:264–9.

    Article  CAS  PubMed  Google Scholar 

  30. Junyaprasert VB, Boonsaner P, Leatwimonlak S, Boonme P. Enhancement of the skin permeation of clindamycin phosphate by Aerosol OT/1-butanol microemulsions. Drug Dev Ind Pharm. 2007;33:874–80.

    Article  CAS  PubMed  Google Scholar 

  31. Talegaonkar S, Akhter S, Jain GK, Ahmad FJ, Khar RK, Jain N, et al. Investigation of nanoemulsion system for transdermal delivery of domperidone: ex-vivo and in-vivo studies. Curr Nanosci. 2008;4:381–90.

    Article  Google Scholar 

  32. Ambade KW, Jadhav SL, Gambhire MN, Kurmi SD, Kadam VJ, Jadhav KR. Formulation and evaluation of flurbiprofen microemulsion. Curr Drug Deliv. 2008;5:32–41.

    Article  CAS  PubMed  Google Scholar 

  33. Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech. 2007;8:E104.

    Article  PubMed  Google Scholar 

  34. Zhao X, Liu JP, Zhang X, Li Y. Enhancement of transdermal delivery of theophylline using microemulsion vehicle. Int J Pharm. 2006;327:58–64.

    Article  CAS  PubMed  Google Scholar 

  35. Paolino D, Ventura CA, Nisticò S, Puglisi G, Fresta M. Lecithin microemulsions for the topical administration of ketoprofen: percutaneous adsorption through human skin and in vivo human skin tolerability. Int J Pharm. 2002;244:21–31.

    Article  CAS  PubMed  Google Scholar 

  36. Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion. J Nanobiotech. 2008;6:8.

    Article  Google Scholar 

  37. Bolzinger MA, Briancon S, Pelletier J, Fessi H, Chevalier Y. Percutaneous release of caffeine from microemulsion, emulsion and gel dosage forms. Eur J Pharm Biopharm. 2008;68:446–51.

    Article  CAS  PubMed  Google Scholar 

  38. Ktistis G, Niopas I. A study on the in-vitro percutaneous absorption of propranolol from disperse systems. J Pharm Pharmacol. 1998;50:413–9.

    CAS  PubMed  Google Scholar 

  39. Gasco MR, Gallarate M, Pattarino F. In vitro permeation of azelaic acid from viscosized microemulsions. Int J Pharm. 1991;69:193–6.

    Article  CAS  Google Scholar 

  40. Abramovi Z, Sustarsic U, Teskac K, Sentjurc M, Kristl J. Influence of nanosized delivery systems with benzyl nicotinate and penetration enhancers on skin oxygenation. Int J Pharm. 2008;359:220–7.

    Article  Google Scholar 

  41. Trotta M. Influence of phase transformation on indomethacin release from microemulsions. J Control Rel. 1999;60:399–405.

    Article  CAS  Google Scholar 

  42. Kriwet K, Muller-Goymann CC. Diclofenac release from phospholipid drug systems and permeation through excised human stratum corneum. Int J Pharm. 1995;125:231–42.

    Article  CAS  Google Scholar 

  43. Zhu W, Yu A, Wang W, Dong R, Wu J, Zhai G. Formulation design of microemulsion for dermal delivery of penciclovir. Int J Pharm. 2008;360:184–90.

    Article  CAS  PubMed  Google Scholar 

  44. Teichmann A, Heuschkel S, Jacobi U, Presse G, Neubert RHH, Sterry W, et al. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Eur J Pharm Biopharm. 2007;67:699–706.

    Article  CAS  PubMed  Google Scholar 

  45. Kreilgaard M, Pedersen EJ, Jaroszewski JW. NMR characterization and transdermal drug delivery potential of microemulsion systems. J Control Rel. 2000;69:421–33.

    Article  CAS  Google Scholar 

  46. Fini A, Bergamante V, Ceschel GC, Ronchi C, De Moraes CA. Control of transdermal permeation of hydrocortisone acetate from hydrophilic and lipophilic formulations. AAPS Pharm Sci Tech. 2008;9:762–8.

    Article  Google Scholar 

  47. Bolzinger MA, Carduner TC, Poelman MC. Bicontinuous sucrose ester microemulsion: a new vehicle for topical delivery of niflumic acid. Int J Pharm. 1998;176:39–45.

    Article  CAS  Google Scholar 

  48. Rhee Y-S, Choi E-S, Park S-C. Transdermal delivery of ketoprofen using microemulsions. Int J Pharm. 2001;228:161–70.

    Article  CAS  PubMed  Google Scholar 

  49. Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSci Tech. 2009;10:69.

    Article  Google Scholar 

  50. Tojo K, Chiang CC, Chien YW. Influence of donor solution upon skin permeation of drug. J Chem Eng Jpn. 1986;19:153–5.

    Article  CAS  Google Scholar 

  51. Azeem A, Iqbal Z, Ahmad FJ, Khar RK, Talegaonkar S. Development and validation of a stability indicating method for determination of ropinirole in the bulk drug and in pharmaceutical dosage forms. Acta Chromat. 2008;20:95–107.

    Article  Google Scholar 

  52. Bergamante V, Ceschel GC, Marazzita S. Effect of vehicles on topical application of aloe vera and arnica montana components. Drug Del. 2007;14:427–32.

    Article  CAS  Google Scholar 

  53. Desai KGH. Enhanced skin permeation of rofecoxib using topical microemulsion gel. Drug Dev Res. 2004;63:33–40.

    Article  CAS  Google Scholar 

  54. Namdeo A, Jain NK. Liquid crystalline pharmacogel based enhanced transdermal delivery of propranolol hydrochloride. J Control Rel. 2002;82:223–36.

    Article  CAS  Google Scholar 

  55. Mutalik S, Udupa N. Glibenclamide transdermal patches: physicochemical, pharmacodynamic, and pharmacokinetic evaluations. J Pharm Sci. 2004;93:1577–94.

    Article  CAS  PubMed  Google Scholar 

  56. Eccleston J. Microemulsions. In: Swarbrick J, Boylan JC, editors. Encyclopedia of pharmaceutical technology, vol. 9. New York: Marcel Dekker; 1994. p. 375–421.

    Google Scholar 

  57. Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000;45:89–121.

    Article  CAS  PubMed  Google Scholar 

  58. Langevin D. Microemulsions. Acc Chem Res. 1988;21:255–60.

    Article  CAS  Google Scholar 

  59. Shah VP. Skin penetration enhancers: scientific perspectives. In: Hsieh DS, editor. Drug permeation enhancement; theory and applications. New York: Marcel Dekker; 1994. p. 19–24.

    Google Scholar 

  60. Alvarez-Figueroa MJ, Blanco-Mendez J. Transdermal delivery of methotrexate: iontophoretic delivery from hydrogels and passive delivery from microemulsions. Int J Pharm. 2001;215:57–65.

    Article  CAS  PubMed  Google Scholar 

  61. Tracharodi D, Rao KP. Transdermal absorption of nifedipine from microemulsions of lipophilic skin penetration enhancers. Int J Pharm. 1994;111:235–41.

    Article  Google Scholar 

  62. Delgado Charro MB, Iglesias Vilas G, Blanco Mendez J, Lopez Quintela MA, Marty JP, Guy RH. Delivery of a hydrophilic solute through the skin from novel microemulsion systems. Eur J Pharm Biopharm. 1997;43:37–42.

    Article  Google Scholar 

  63. Junyaprasert VB, Boonme P, Songkro S, Kravel K, Rades T. Transdermal delivery of hydrophobic and hydrophilic local anaesthetics from o/w and w/o Brij 97-based microemulsions. J Pharm Pharmaceut Sci. 2007;10:319–29.

    Google Scholar 

  64. Changez M, Varshney M, Chander J, Dinda AK. Effect of the composition of lecithin/n-propanol/isopropyl myristate/water microemulsions on barrier properties of mice skin for transdermal permeation of tetracaine hydrochloride: in vitro. Colloids Surf B: Biointerfaces. 2006;50:18–25.

    Article  CAS  Google Scholar 

  65. Yun SR, Jung SP, San CC. Transdermal delivery of ketoprofen using microemulsions. Int J Pharm. 2001;228:161–70.

    Article  Google Scholar 

  66. Rage BD, Kao JP, Polli JE. Effects of nonionic surfactants on membrane transporters in caco-2 cell monolayers. Eur J Pharm Sci. 2002;16:237–46.

    Article  Google Scholar 

  67. Hua L, Weisan P, Jiayu L, Ying Z. Preparation, evaluation and NMR characterization of vinpocetine microemulsion for transdermal delivery. Drug Dev Ind Pharm. 2004;30:657–66.

    Article  CAS  PubMed  Google Scholar 

  68. Mou D, Chen H, Du D, Mao C, Wan J, Xu H, et al. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int J Pharm. 2008;353:270–76.

    Article  CAS  PubMed  Google Scholar 

  69. Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm. 2006;315:52–8.

    Article  CAS  PubMed  Google Scholar 

  70. Spiclin P, Homar M, Zupancic-Valant A. Sodium ascorbyl phosphate for topical microemulsions. Int J Pharm. 2003;256:65–73.

    Article  CAS  PubMed  Google Scholar 

  71. Valenta C, Schultz K. Influence of carrageenan on the rheology and skin permeation of microemulsion formulations. J Control Rel. 2004;95:257–67.

    Article  CAS  Google Scholar 

  72. Bonacucina G, Martelli S, Palmieri GF. Rheological, mucoadhesive and release properties of carbopol gels in hydrophilic cosolvents. Int J Pharm. 2004;282:115–30.

    Article  CAS  PubMed  Google Scholar 

  73. Lapasin R, Grassi M, Coceani N. Effect of polymer addition on the rheology of o/w microemulsions. Rheol Acta. 2001;40:185–192.

    Article  CAS  Google Scholar 

  74. Draize JH, Woodward G, Calvery HO. Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther. 1944;82:377–90.

    CAS  Google Scholar 

Download references

Acknowledgments

The authors are indebted to the University Grants Commission, Govt. of India for providing the financial assistance to the project (project no. F.31-74/2005 SR). Adnan Azeem thanks the Colocon Asia for providing gift samples of surfactants and oils (Gattefosse, France) and USV (Mumbai, India) for the gift sample of ropinirole. The authors also wish to thank the Sophisticated Analytical Instruments Facilities (SAIF) of All India Institute of Medical Sciences (AIIMS), New Delhi, India for carrying out the TEM analysis.

Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, 110062, India

    Adnan Azeem, Farhan J. Ahmad, Roop K. Khar & Sushama Talegaonkar

Authors
  1. Adnan Azeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farhan J. Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roop K. Khar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sushama Talegaonkar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adnan Azeem.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Azeem, A., Ahmad, F.J., Khar, R.K. et al. Nanocarrier for the Transdermal Delivery of an Antiparkinsonian Drug. AAPS PharmSciTech 10, 1093–1103 (2009). https://doi.org/10.1208/s12249-009-9306-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9306-2

Key words

Search

Navigation