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Effect of formulation pH on transport of naltrexone species and pore closure in microneedle-enhanced transdermal drug delivery Priyanka Ghosh, Nicole K. Brogden, and Audra L Stinchcomb Mol. Pharmaceutics, Just Accepted Manuscript • DOI: 10.1021/mp3007083 • Publication Date (Web): 16 Apr 2013 Downloaded from http://pubs.acs.org on April 29, 2013
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Molecular Pharmaceutics
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Effect of formulation pH on transport of naltrexone species and pore closure in microneedle-
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enhanced transdermal drug delivery
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Priyanka Ghosh a,b, Nicole K. Brogden a,c and Audra L. Stinchcomb a,b,d*
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a
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KY 40536-0082, USA
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b
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21201, USA
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c
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University of Iowa, Iowa City, IA-52242, USA (Current address)
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d
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington,
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy,
AllTranz, Inc., Lexington, KY 40505, USA
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Corresponding author
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Audra L. Stinchcomb, PhD
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Professor, Department of Pharmaceutical Sciences
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University of Maryland School of Pharmacy
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20 N. Pine St.
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Baltimore, MD 21201, USA
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Phone: (410) 706 – 2646
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Fax: (410) 706 – 0886
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Email:
[email protected] 22 1 ACS Paragon Plus Environment
Molecular Pharmaceutics
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Abstract:
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Microneedle-enhanced
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pharmacologically active molecules that can be transported across the skin. Formulation pH
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plays an important role in all drug delivery systems; however, for transdermal delivery it
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becomes specifically significant since a wide range of pH values can be exploited for patch
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formulation as long as it does not lead to skin irritation or sensitization issues. Wound healing
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literature has shown significant pH effects on barrier recovery. Stability and solubility of the
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drug, and thus transport across skin are all affected by formulation pH. The current study
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examined the role of ionization state of the drug naltrexone on transdermal flux and permeability
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across microneedle treated skin, as compared to intact skin. Impedance spectroscopy was done
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in pigs in vivo to assess the role of formulation pH on the rate of micropore closure under the
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influence of three different pH conditions. The data indicated that while there was significant
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advantage of using a lower pH formulation in terms of total transport across microneedle treated
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skin, the pH however did not have any significant effect on the rate of micropore closure beyond
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the first 24 hours.
transdermal
drug
delivery
greatly
improves
the
subset
of
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Molecular Pharmaceutics
Table of contents graphic
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Keywords:
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Microneedle, micropore closure, permeability, transdermal, impedance spectroscopy
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Introduction:
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Skin is the largest and the most accessible organ of the body. The extensive vasculature
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in the dermal region of the skin ensures rapid uptake of any compound that is transported
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across the skin into the systemic circulation, thus making the skin a very attractive drug delivery
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target
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xenobiotics as well as excessive water loss, the stratum corneum (SC), the topmost layer of the
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skin is specifically designed to protect the human body
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pharmacologically active molecules can successfully cross the SC (passive delivery) in
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therapeutically relevant concentrations
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has focused primarily on small molecular weight (
