Heat therapy is widely used for pain relief and may unintentionally be used in conjunction with pain relieving topical formulations. The purpose of this study was to evaluate the influence of heat on the permeation of diclofenac through porcine and human skin, comparing four marketed products.
In vitro permeation tests (IVPT) were performed on porcine skin from a single miniature pig and human skin from three donors. Skin temperature was maintained at either 32 ± 1°C or 42 ± 1°C to mimic normal and elevated skin temperature conditions, respectively.
IVPT studies on porcine and human skin were able to demonstrate heat-induced enhancement in flux and cumulative amount of drug permeated from the four diclofenac products. The pivotal data showed the most significant heat-induced enhancement for the solution, followed by the patch and two gels in decreasing order of significance based on p values. Diclofenac solution showed the highest flux and cumulative amount permeated at both baseline and elevated skin temperature compared to the patch and gels.
The studies demonstrated that exposure to heat can alter drug permeation from topical formulations, but the increased levels are not expected to lead to systemic concentrations that are of concern. Formulation design and excipients can influence drug permeation at elevated skin temperature.
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Analysis of variance
Active pharmaceutical ingredient
Controlled heat-aided drug delivery
NCI Cooperative Human Tissue Network
- Cmax :
High-performance liquid chromatography
In vitro permeation test
- Jmax :
Lower limit of quantification
Logarithm of octanol-water partition coefficient
Acid dissociation constant
- SC :
Transepidermal water loss
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ACKNOWLEDGMENTS AND DISCLOSURES
Funding for this project was made possible, in part, by the Food and Drug Administration through grant U01FD004955. 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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Thomas, S., Shin, S.H., Hammell, D.C. et al. Effect of Controlled Heat Application on Topical Diclofenac Formulations Evaluated by In Vitro Permeation Tests (IVPT) Using Porcine and Human Skin. Pharm Res 37, 49 (2020). https://doi.org/10.1007/s11095-019-2741-1
- drug permeation