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Advanced harmonization techniques result in accurate establishment of in vitro–in vivo correlations for oxybenzone from four complex dermal formulations with reapplication

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Abstract

Due to high variability during clinical pharmacokinetic (PK) evaluation, the prediction of in vivo exposure from in vitro absorption testing of topical semisolid and liquid dermal products has historically proven difficult. Since absorption from unoccluded formulations can be influenced by environmental factors such as temperature and humidity, maximal effort must be placed on the harmonization of experimental parameters between in vitro and in vivo testing conditions to establish accurate in vitro/in vivo correlations (IVIVC). Using four different sunscreen formulations as a model, we performed in vitro permeation testing (IVPT) studies with excised human skin and maintained strict harmonization techniques to control application time, occlusion, temperature, and humidity during in vivo human serum PK evaluation. The goal was to investigate if increased control over experimental parameters would result in decreased inter-subject variability of common topical formulations leading to acceptable IVIVC establishment. Using a deconvolution-based approach, excellent point-to-point (Level A correlation) IVIVC for the entire 12-h study duration was achieved for all four sunscreen formulations with < 10% prediction error of both area under the curve (AUC) and peak concentration (Cmax) estimation. The low variability of in vivo absorption data presents a proof-of-concept protocol design for testing of complex semisolid and liquid topical formulations applied over a large surface area with reapplication in a reliable manner. This work also presents the opportunity for expanded development of testing for the impact of altered temperature and humidity conditions on product absorption in vivo with a high degree of precision.

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Acknowledgements

We are grateful for the efforts of Jennifer Marron and other personnel at the General Clinical Research Center at the University of Maryland as well as Danielle Fox for her endless guidance on clinical study management. Recruitment for the study included/was done via ResearchMatch, a national health volunteer registry that was created by several academic institutions and supported by the U.S. National Institutes of Health as part of the Clinical Translational Science Award (CTSA) program. ResearchMatch has a large population of volunteers who have consented to be contacted by researchers about health studies for which they may be eligible. Review and approval for this study and all procedures was obtained from the University of Maryland, Baltimore Institutional Review Board. Biospecimens were provided by the NCI funded Cooperative Human Tissue Network (CHTN). Other investigators may have received specimens from the same tissue specimens. The CHTN is comprised of six academic institutions who collect and distribute remnant human biospecimens from routine surgical and autopsy procedures to investigators for basic and applied science to advance biomedical research.

Funding

Funding for this project was made possible, in part, by the University of Maryland Baltimore, School of Pharmacy Mass Spectrometry Center (Research Award SOP1841-IQB2014), the University of Maryland Baltimore, Institute for Clinical & Translational Research (ICTR) voucher program, and the University of Maryland Baltimore Pharmaceutical Sciences Department Fellowship and Merit Awards.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 North Pine Street, Baltimore, MD, 21201, USA

    Paige N. Zambrana, Dana C. Hammell & Audra L. Stinchcomb

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  1. Paige N. Zambrana
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Contributions

Paige Zambrana: writing–original draft; data curation; formal analysis; investigation; methodology; validation; visualization. Dana C. Hammell: writing–review and editing; data curation; project administration; resources. Audra L. Stinchcomb: conceptualization; funding acquisition; methodology; supervision; writing–review and editing

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Correspondence to Audra L. Stinchcomb.

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The University of Maryland, Baltimore Investigational Review Board provided approval for protocol and informed consents for subjects in accordance with the Code of Federal Regulations and local requirements. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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Zambrana, P.N., Hammell, D.C. & Stinchcomb, A.L. Advanced harmonization techniques result in accurate establishment of in vitro–in vivo correlations for oxybenzone from four complex dermal formulations with reapplication. Drug Deliv. and Transl. Res. 13, 275–291 (2023). https://doi.org/10.1007/s13346-022-01186-7

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