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Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging
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Percutaneous penetration modifiers and formulation effects.

Diksha Kaushik1, Aurora Costache, Bozena Michniak-Kohn

  • 1Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, NJ 08854, United States.

International Journal of Pharmaceutics
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The vehicle used significantly impacts how penetration modifiers affect skin permeation of diethyl-m-toluamide (DEET). An enhancer can become a retardant, and vice versa, depending on the formulation.

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Area of Science:

  • * Pharmaceutical Sciences
  • * Dermal Drug Delivery
  • * Chemical Engineering

Background:

  • * Percutaneous permeation of active ingredients like diethyl-m-toluamide (DEET) is crucial for topical and transdermal applications.
  • * Understanding how formulation vehicles influence penetration modifiers is key to optimizing drug delivery.
  • * Existing terminology may not fully capture the dual role of these modifiers.

Purpose of the Study:

  • * To investigate the impact of different vehicles on the enhancement or retardation of DEET permeation by five penetration modifiers.
  • * To explore the interaction between penetration modifiers and stratum corneum ceramides using chemical modeling.
  • * To propose the term "penetration modifiers" to encompass compounds that can enhance or retard skin permeation.

Main Methods:

  • * In vitro permeation studies of DEET across skin models using various penetration modifiers (laurocapram, N-0915, DMBIS, DMMCBI, TBDOC).
  • * Formulations were prepared using different vehicles: water, propylene glycol (PG), ethanol, and polyethylene glycol 400 (PEG 400).
  • * Chemical modeling was employed to study modifier interactions with stratum corneum ceramide.

Main Results:

  • * Laurocapram enhanced DEET permeation in PG but retarded it in PEG 400.
  • * N-0915 acted as a retardant in ethanol and PEG 400, but not in water.
  • * DMBIS and DMMCBI showed retardant effects with ethanol, while TBDOC acted as a retardant in ethanol but an enhancer in water, PG, and PEG 400.

Conclusions:

  • * The effect of a penetration modifier on DEET permeation is highly dependent on the formulation vehicle.
  • * An enhancer in one vehicle can function as a retardant in another, and vice versa.
  • * The term "penetration modifiers" is more appropriate for these compounds due to their variable effects.