Effect of Controlled Heat Application on Topical Diclofenac Formulations Evaluated by In Vitro Permeation Tests (IVPT) Using Porcine and Human Skin

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2020 Feb 9

PMID 32034502

Citations 3

Authors

Sherin Thomas

Soo Hyeon Shin

Dana C Hammell

Hazem E Hassan

Audra L Stinchcomb

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Citing Articles

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In Vitro-In Vivo Correlation of Buprenorphine Transdermal Systems Under Normal and Elevated Skin Temperature.

Thomas S, Hammell D, Hassan H, Stinchcomb A Pharm Res. 2023; 40(5):1249-1258.

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Optimization and Evaluation of the In Vitro Permeation Parameters of Topical Products with Non-Steroidal Anti-Inflammatory Drugs through Strat-M Membrane.

Milanowski B, Wosicka-Frackowiak H, Glowka E, Sosnowska M, Wozny S, Stachowiak F Pharmaceutics. 2021; 13(8).

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References

Shomaker T, Zhang J, Ashburn M . Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. Pain Med. 2004; 1(3):225-30. DOI: 10.1046/j.1526-4637.2000.00030.x. View

Klemsdal T, Gjesdal K, Bredesen J . Heating and cooling of the nitroglycerin patch application area modify the plasma level of nitroglycerin. Eur J Clin Pharmacol. 1992; 43(6):625-8. DOI: 10.1007/BF02284961. View

Peck K, Ghanem A, Higuchi W . The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membrane. J Pharm Sci. 1995; 84(8):975-82. DOI: 10.1002/jps.2600840813. View

Barkve T, Langseth-Manrique K, Bredesen J, Gjesdal K . Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature. Am Heart J. 1986; 112(3):537-41. DOI: 10.1016/0002-8703(86)90518-1. View

Chantasart D, Chootanasoontorn S, Suksiriworapong J, Li S . Investigation of pH Influence on Skin Permeation Behavior of Weak Acids Using Nonsteroidal Anti-Inflammatory Drugs. J Pharm Sci. 2015; 104(10):3459-70. DOI: 10.1002/jps.24556. View

Rose P, Macfee M, Boswell M . Fentanyl transdermal system overdose secondary to cutaneous hyperthermia. Anesth Analg. 1993; 77(2):390-1. DOI: 10.1213/00000539-199308000-00029. View

Marra D, Yip D, Fincher E, Moy R . Systemic toxicity from topically applied lidocaine in conjunction with fractional photothermolysis. Arch Dermatol. 2006; 142(8):1024-6. DOI: 10.1001/archderm.142.8.1024. View

Trommer H, Neubert R . Overcoming the stratum corneum: the modulation of skin penetration. A review. Skin Pharmacol Physiol. 2006; 19(2):106-21. DOI: 10.1159/000091978. View

Sintov A . Cumulative evidence of the low reliability of frozen/thawed pig skin as a model for in vitro percutaneous permeation testing. Eur J Pharm Sci. 2017; 102:261-263. DOI: 10.1016/j.ejps.2017.03.024. View

10.

Shin S, Ghosh P, Newman B, Hammell D, Raney S, Hassan H . On the Road to Development of an in Vitro Permeation Test (IVPT) Model to Compare Heat Effects on Transdermal Delivery Systems: Exploratory Studies with Nicotine and Fentanyl. Pharm Res. 2017; 34(9):1817-1830. DOI: 10.1007/s11095-017-2189-0. View

11.

McGettigan P, Henry D . Use of non-steroidal anti-inflammatory drugs that elevate cardiovascular risk: an examination of sales and essential medicines lists in low-, middle-, and high-income countries. PLoS Med. 2013; 10(2):e1001388. PMC: 3570554. DOI: 10.1371/journal.pmed.1001388. View

12.

Shin S, Thomas S, Raney S, Ghosh P, Hammell D, El-Kamary S . In vitro-in vivo correlations for nicotine transdermal delivery systems evaluated by both in vitro skin permeation (IVPT) and in vivo serum pharmacokinetics under the influence of transient heat application. J Control Release. 2017; 270:76-88. DOI: 10.1016/j.jconrel.2017.11.034. View

13.

Treffel P, Muret P, Coumes-Marquet S, Agache P . Effect of occlusion on in vitro percutaneous absorption of two compounds with different physicochemical properties. Skin Pharmacol. 1992; 5(2):108-13. DOI: 10.1159/000211027. View

14.

Prodduturi S, Sadrieh N, Wokovich A, Doub W, Westenberger B, Buhse L . Transdermal delivery of fentanyl from matrix and reservoir systems: effect of heat and compromised skin. J Pharm Sci. 2009; 99(5):2357-66. DOI: 10.1002/jps.22004. View

15.

Cordery S, Pensado A, Chiu W, Shehab M, Bunge A, Delgado-Charro M . Topical bioavailability of diclofenac from locally-acting, dermatological formulations. Int J Pharm. 2017; 529(1-2):55-64. PMC: 5557682. DOI: 10.1016/j.ijpharm.2017.06.063. View

16.

Petersen K, Rousing M, Jensen C, Arendt-Nielsen L, Gazerani P . Effect of local controlled heat on transdermal delivery of nicotine. Int J Physiol Pathophysiol Pharmacol. 2011; 3(3):236-42. PMC: 3175749. View

17.

Akomeah F, Nazir T, Martin G, Brown M . Effect of heat on the percutaneous absorption and skin retention of three model penetrants. Eur J Pharm Sci. 2004; 21(2-3):337-45. DOI: 10.1016/j.ejps.2003.10.025. View

18.

Shomaker T, Zhang J, Ashburn M . A pilot study assessing the impact of heat on the transdermal delivery of testosterone. J Clin Pharmacol. 2001; 41(6):677-82. DOI: 10.1177/00912700122010447. View

19.

Marriott T, Charney M, Stanworth S . Effects of application durations and heat on the pharmacokinetic properties of drug delivered by a lidocaine/tetracaine patch: a randomized, open-label, controlled study in healthy volunteers. Clin Ther. 2012; 34(10):2174-83. DOI: 10.1016/j.clinthera.2012.08.008. View

20.

Brown M, Jones S . Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin. J Eur Acad Dermatol Venereol. 2005; 19(3):308-18. DOI: 10.1111/j.1468-3083.2004.01180.x. View