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The AAPS Journal

, 21:70 | Cite as

Skin Delivery and Irritation Potential of Phenmetrazine as a Candidate Transdermal Formulation for Repurposed Indications

  • Ying Jiang
  • Kevin S. Murnane
  • Sonalika A. Bhattaccharjee
  • Bruce E. Blough
  • Ajay K. BangaEmail author
Research Article

Abstract

Phenmetrazine, a selective dopamine and norepinephrine releaser, previously available as an oral anorectic, is prone to be abused. This study aimed to assess the feasibility of delivering phenmetrazine via the transdermal route for a new indication, while also minimizing its abuse potential. The passive permeation of phenmetrazine through dermatomed human cadaver skin was evaluated using static Franz diffusion cells at 10 mg/mL for the fumarate salt, and at 20, 40, and 80 mg/mL for the free base in propylene glycol for 24 h. Further, oleic acid (5% w/w), oleyl alcohol (5% and 10% w/w), and lauric acid (10% w/w) were investigated as chemical permeation enhancers to enhance the delivery. Skin irritation potential was assessed using EpiDerm™ in vitro reconstructed human epidermal model. The free base showed superior 24-h delivery (8.13 ± 4.07%, 10.6 ± 2.5%, and 10.4 ± 1.4% for groups with 20, 40, and 80 mg/mL of the free base, respectively) to phenmetrazine fumarate salt (undetectable). The successful screening of effective chemical enhancers, oleyl alcohol (5% and 10% w/w), oleic acid (5% w/w), and lauric acid (10% w/w) resulted in significant enhancement of delivery. The calculated therapeutic relevant flux for the potential indication, attention deficit hyperactivity disorder, 20 μg/cm2/h was met, where a 24-mg daily dose from a 50-cm2 patch was projected to be delivered to a 60-kg individual. Irritation study results suggest that formulations with therapeutically relevant delivery are likely to be non-irritant. In conclusion, it is feasible to deliver therapeutically relevant amounts of phenmetrazine via the transdermal route.

KEY WORDS

Chemical permeation enhancers Phenmetrazine Transdermal delivery Skin irritation 

Notes

Funding information

These studies were supported by the Georgia Research Alliance based in Atlanta, Georgia, by grant number GRA.VL17.11 (Murnane and Banga—Multiple Principal Investigators) as well as by the National Institute on Drug Abuse by grant number DA12970 (Blough—Principal Investigator).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Ying Jiang
    • 1
  • Kevin S. Murnane
    • 1
  • Sonalika A. Bhattaccharjee
    • 1
  • Bruce E. Blough
    • 2
  • Ajay K. Banga
    • 1
    Email author
  1. 1.Center for Drug Delivery Research, Department of Pharmaceutical Sciences, College of PharmacyMercer UniversityAtlantaUSA
  2. 2.Center for Drug Discovery, Research Triangle InstituteResearch Triangle ParkDurhamUSA

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