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Development of a codrug approach for sustained drug delivery across microneedle-treated skin

Authors

  • Priyanka Ghosh,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky
    Current affiliation:
    1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201.
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  • Raghotham R. Pinninti,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky
    Current affiliation:
    1. HDH Pharma Inc., Morrisville, North Carolina–27560.
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  • Dana C. Hammell,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky
    2. AllTranz, Inc. Lexington, 40505 Kentucky
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  • Kalpana S. Paudel,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky
    Current affiliation:
    1. Department of Pharmaceutical Sciences, South College School of Pharmacy, Knoxville, Tennessee 37922
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  • Audra L. Stinchcomb

    Corresponding author
    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky
    2. AllTranz, Inc. Lexington, 40505 Kentucky
    Current affiliation:
    1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201.
    • Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082 Kentucky. Telephone: +410-706-2646; Fax: +410-706-0886
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Abstract

Microneedle (MN) enhanced transdermal drug delivery enables the transport of a host of molecules that cannot be delivered across the skin by passive diffusion alone. However, the skin being a self-regenerating organ heals itself and thus prevents delivery of molecules through micropores for a 7-day time period, the ideal transdermal delivery goal. Hence, it is necessary to employ a second drug molecule, a cyclooxygenase inhibitor to enhance pore lifetime by decreasing local subclinical inflammatory response following MN treatment. A codrug approach using a 3-O-ester codrug of the model drug naltrexone (NTX) with diclofenac (DIC), a cyclooxygenase inhibitor, was tested in vitro as well as in vivo to look at stability, bioconversion and permeation. The results indicated that the approach could be useful for transdermal drug delivery of NTX from a single patch for a week, but stability and solubility optimization will be required for the codrug before it can deliver significant levels of NTX into the plasma. The skin concentration of DIC was high enough to keep the pores open in vivo in a hairless guinea pig model as demonstrated by day seven pore visualization studies. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1458–1467, 2013

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