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AAPS PharmSciTech

, Volume 19, Issue 7, pp 2778–2786 | Cite as

The Sensitivity of In Vitro Permeation Tests to Chemical Penetration Enhancer Concentration Changes in Fentanyl Transdermal Delivery Systems

  • Soo Hyeon Shin
  • Jukkarin Srivilai
  • Sarah A. Ibrahim
  • Caroline Strasinger
  • Dana C. Hammell
  • Hazem E. Hassan
  • Audra L. Stinchcomb
Research Article Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model
Part of the following topical collections:
  1. Theme: Team Science and Education for Pharmaceuticals: the NIPTE Model

Abstract

Chemical penetration enhancers (CPEs) are frequently incorporated into transdermal delivery systems (TDSs) to improve drug delivery and to reduce the required drug load in formulations. However, the minimum detectable effect of formulation changes to CPE-containing TDSs using in vitro permeation tests (IVPT), a widely used method to characterize permeation of topically applied drug products, remains unclear. The objective of the current exploratory study was to investigate the sensitivity of IVPT in assessing permeation changes with CPE concentration modifications and subsequently the feasibility of IVPT’s use for support of quality control related to relative CPE concentration variation in a given formulation. A series of drug-in-adhesive (DIA) fentanyl TDSs with different amounts of CPEs were prepared, and IVPT studies utilizing porcine and human skin were performed. Although IVPT could discern TDSs with different amounts of CPE by significant differences in flux profiles, maximum flux (Jmax) values, and total permeation amounts, the magnitudes of the CPE increment needed to see such significant differences were very high (43–300%) indicating that IVPT may have limitations in detecting small changes in CPE amounts in some TDSs. Possible reasons for such limitations include formulation polymer and/or other excipients, type of CPE, variability associated with IVPT, skin type used, and disrupted stratum corneum (SC) barrier effects caused by CPEs.

KEY WORDS

chemical penetration enhancer (CPE) transdermal delivery system (TDS) in vitro permeation test (IVPT) fentanyl 

Abbreviations

API

Active pharmaceutical ingredient

CPE

Chemical penetration enhancer

DPG

Dipropylene glycol

FDA

Food and Drug Administration

HPLC

High-performance liquid chromatography

IPM

Isopropyl myristate

IVPT

In vitro permeation test

Jmax

Maximum flux

LLOQ

Lower limit of quantification

OA

Oleic acid

OLA

Oleyl alcohol

PIB

Polyisobutylene

PSA

Pressure-sensitive adhesive

SC

Stratum corneum

TDS

Transdermal delivery system

TEWL

Transepidermal water loss

Notes

Acknowledgements

We thank Dr. Nihar Shah for his valuable guidance in TDS formulations. We also thank 3M for providing various samples of release liners and backings, Henkel Corporation and Dow Corning for providing PSAs, and Croda Inc. for providing various chemical penetration enhancer samples.

Funding

Funding for this project was made possible, in part, by the Food and Drug Administration through grant 5U01FD004275-05 (Subaward NIPTE-U01-MD-2016-003-001).

The views expressed in this paper do not reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Soo Hyeon Shin
    • 1
  • Jukkarin Srivilai
    • 2
  • Sarah A. Ibrahim
    • 3
  • Caroline Strasinger
    • 3
  • Dana C. Hammell
    • 1
  • Hazem E. Hassan
    • 1
    • 4
  • Audra L. Stinchcomb
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of MarylandBaltimoreUSA
  2. 2.Department of Cosmetic Sciences, School of Pharmaceutical SciencesUniversity of PhayaoPhayaoThailand
  3. 3.Office of Pharmaceutical Quality, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringUSA
  4. 4.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyHelwan UniversityCairoEgypt

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