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Comparative Study
. 2015;41(7):1089-94.
doi: 10.3109/03639045.2014.927481. Epub 2014 Dec 8.

Trans-ungual delivery of itraconazole hydrochloride by iontophoresis

Avadhesh Kushwaha  1 , Melissa Jacob, H N Shiva Kumar, Shobharani Hiremath, Sacchidanand Aradhya, Michael A Repka, S Narasimha Murthy
Affiliations
Comparative Study

Trans-ungual delivery of itraconazole hydrochloride by iontophoresis

Avadhesh Kushwaha et al. Drug Dev Ind Pharm. 2015.

Abstract

Itraconazole (ITR) is a potent antifungal drug. However, poor aqueous solubility limits its permeation ability across the human nail plate. Therefore, in this project, ITR was converted to hydrochloride salt (ITR-HCl) to improve its solubility and to render it amenable to iontophoresis. ITR-HCl was characterized by spectroscopic methods and antifungal efficacy was evaluated in comparison to the base. In vitro and ex vivo transport studies (passive and iontophoresis) were carried out across the porcine hoof membrane and excised human cadaver toe using two different protocols; continuous delivery of drug for 24 h and pulsed delivery of drug for 3 days (8 h/day). The antifungal efficacy of ITR-HCL was comparable to ITR. Iontophoresis was found to be more effective than passive mode of delivery of ITR-HCL. In both iontophoresis as well as passive mode of delivery, the pulsed protocol resulted in more ungual and trans-ungual delivery of drug than continuous protocol. ITR-HCL could be delivered into and across the nail plate by iontophoresis. Human cadaver toe appears to be a good model to investigate the ungual delivery of drugs.

Keywords: Cadaver toe; iontophoresis; itraconazole; itraconazole hydrochloride; porcine hoof membrane.

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Conflict of interest statement

Declaration of interest

This project was partially funded by a grant number AI 27094 from National Institute of Allergyand Infectious Diseases (NIAID). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Figures

Figure 1
Figure 1
DSC (PerkinElmer, San Jose, CA) thermogram of ITR and ITR–HCl.
Figure 2
Figure 2
Correlation between amount of drug retained in the nail plate and amount of drug retained in the hoof membrane after transport studies.
Figure 3
Figure 3
Correlation between amount of drug permeated across the nail plate and amount of drug permeated across the hoof membrane.
See this image and copyright information in PMC

References

    1. Elewski BE. Onychomycosis: pathogenesis, diagnosis, and management. Clin Microbiol Rev. 1998;11:415–29. - PMC - PubMed
    1. Hao J, Smith KA, Li SK. Iontophoretically enhanced ciclopirox delivery into and across human nail plate. J Pharm Sci. 2009;98:3608–16. - PMC - PubMed
    1. Murdan S. Drug delivery to the nail following topical application. Int J Pharm. 2002;236:1–26. - PubMed
    1. Murthy SN, Waddell DC, Shivakumar HN, et al. Iontophoretic permselective property of human nail. J Dermatol Sci. 2007;46:150–2. - PubMed
    1. Nair AB, Kim HD, Chakraborty B, et al. Ungual and trans-ungual iontophoretic delivery of terbinafine for the treatment of onychomycosis. J Pharm Sci. 2009;98:4130–40. - PubMed

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