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In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems

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Abstract

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P < 0.001) higher than that with product-C, product-A, gel, and spray. However, products-A and C, gel, and spray showed almost the same (P > 0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P < 0.001) higher than those with products-A and B, gel, and spray. The in vitro study results indicate a high potential of skin-to-skin drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

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Abbreviations

ANOVA:

Analysis of variance

DRE:

Drug retention in human epidermis

CDER:

Center for Drug Evaluation and Research

CHTN:

Cooperative Human Tissue Network

DIA:

Drug-in-adhesive

HSE:

Heat separated human epidermis

HT:

Hormone therapy

Kp:

Permeability coefficient

NDRI:

National Disease Research Interchange

PSA:

Pressure-sensitive adhesive

Q24 :

Drug permeated at the end of 24 h

SC:

Stratum corneum

TDDS:

Transdermal drug delivery systems

TEWL:

Transepidermal water loss

VVA:

Vulvovaginal atrophy

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ACKNOWLEDGEMENTS

This work was supported by the FDA Office of Women’s Health. This project was supported in part by an appointment to the ORISE Research Participation Program at the Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and FDA/CDER. The authors acknowledge the help of Robert Hunt (CDER/OPQ/OTR/DPQR) in conducting some of the experiments. Surgically discarded human skin samples were provided by Cooperative Human Tissue Network which is funded by National Cancer Institute (other investigators may have received the specimens from the same subjects).

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  1. Mansoor A. Khan

    Present address: Rangel College of Pharmacy, Texas A&M University Health Science Center, College Station, Texas, USA

Authors and Affiliations

  1. Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    Yellela S. R. Krishnaiah, Naresh Pavurala, Yang Yang, Prashanth Manda, Usha Katragadda, Yongsheng Yang, Rakhi Shah & Mansoor A. Khan

  2. Division of Bone, Reproductive and Urology Products, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA

    Guodong Fang

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  1. Yellela S. R. Krishnaiah
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Correspondence to Yellela S. R. Krishnaiah.

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Krishnaiah, Y.S.R., Pavurala, N., Yang, Y. et al. In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems. AAPS PharmSciTech 18, 2131–2140 (2017). https://doi.org/10.1208/s12249-016-0694-9

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