The history of transdermal patches: from Antiquity to the modern era

The administration of medicinal substances through the skin has been documented since Antiquity. Plasters and ointments were initially used to treat local conditions, and some preparations were capable of producing effects on the body beyond the site of application. Over the centuries, empirical observation was gradually supplemented by scientific studies on skin physiology and the formulation of these preparations, making it possible to identify the factors influencing the absorption of substances applied to the skin. This body of knowledge led, in the twentieth century, to the development of modern transdermal systems, based on an understanding of the properties of active ingredients and controlled-release mechanisms. The history of transdermal patches thus illustrates the transition from ancient empirical practices to contemporary pharmaceutical devices [1]. 

From Antiquity to the Nineteenth Century: The origins of a therapeutic intuition 

The use of remedies applied to the skin is an extremely ancient medical practice. The earliest archaeological evidence indicates that certain mixtures were used both to adorn and to protect the skin. A well-known example is ochre found in the Blombos Cave in South Africa, dated to approximately 100,000 years ago, illustrating this dual function [2]. Later, around 4,000 BCE, the Sumerians left written records of the use of cutaneous preparations on clay tablets, representing one of the earliest known documentations of topical remedies [3]. 

In ancient Egypt, cutaneous preparations developed considerably. Vegetable oils such as castor, olive, or sesame oil, along with animal fats, bitter almond, peppermint, or rosemary, were combined to produce ointments, creams, salves, and poultices [4]. 

The Ebers Papyrus, dated around 1550 BCE, lists more than 800 prescriptions, including topical applications intended to treat skin conditions such as burns, wounds, or blisters. Some preparations were also designed to produce systemic effects, such as the topical application of frankincense to relieve headaches. The importance of topical treatments is evidenced by depictions of ointment-making workshops in numerous Egyptian tombs [3]. 

A few centuries later, Galen, a Greek physician of the 2nd century CE and often regarded as the “father of pharmacy,” described preparations combining medicinal plants with excipients, representing one of the earliest examples of structured galenic formulations. These mixtures aimed to facilitate application and optimize the effectiveness of active substances, marking a significant step in the history of pharmaceutical formulation [5]. 

In ancient China, transcutaneous plasters combining plants with adhesive bases on fabric or paper appeared as the ancestors of modern patches. In Europe, Western plasters generally contained a single active ingredient, such as nicotine in the 16th-century Emplastrum opodeldoch [3]. 

In the 11th century, Avicenna, the renowned Persian physician, compiled in his book Canon of Medicine a collection of preparations, including topical remedies [6]. Later, during the Renaissance, the use of mercurial ointments to treat syphilis illustrates the continuity of transdermal practices and their gradual evolution toward more structured formulations [7]. 

Questioning transdermal applications at the end of the 19th Century 

By the late 19th century, medicated plasters were widely used, some for local effects, others intended for systemic action, with substances such as peppermint, belladonna, or poisonous hemlock. Certain products were specifically designed for cutaneous use, such as those containing mercury or cantharides [3]. 

However, the efficacy of these preparations remained debated. While some cases showed that substances could penetrate the skin, many still considered intact skin to be impermeable. This controversy marked a period of critical reassessment of transdermal products [1]. 

From the 20th Century to the modern era: toward a scientific understanding of the transdermal route 

Following the period of skepticism observed at the end of the 19th century, the early 20th century marked a major evolution in understanding the skin as a route of administration. Gradually, the notion of an entirely impermeable skin barrier was abandoned in favor of a more nuanced view, recognizing selective permeability, particularly for certain lipophilic substances [3]. 

This shift relied largely on clinical and toxicological observations. In the early 1900s, several cases of systemic poisoning resulting from accidental skin exposure were reported, notably among children exposed to dyes or chemical substances present in textiles or industrial products. These events unintentionally highlighted the ability of certain molecules to penetrate the skin barrier and reach systemic circulation [3]. 

At the same time, the first in vivo studies aiming to demonstrate percutaneous absorption began to appear. These studies relied on the analysis of blood or urine after skin application, using essentially qualitative methods. The presence of substances was then evidenced through changes in color, acidity, or density of the samples, providing the first experimental proof of systemic absorption via the skin [8]. 

Throughout the 20th century, several clinical observations played a decisive role in understanding the absorption of substances through the skin. The penetration of nitroglycerin was first highlighted by the occurrence of adverse effects in workers exposed in industrial settings, before being harnessed in a controlled manner for therapeutic purposes [9]. Similar observations were reported for nicotine, as well as for certain steroid hormones, whose cutaneous absorption was revealed following occupational exposure [10], [11]. 

Although often incidental, these findings were crucial in identifying the physicochemical characteristics that favor transdermal passage of molecules. They laid the scientific foundation for the development of modern transdermal systems, which gradually emerged as fully recognized galenic formulations during the second half of the 20th century [1]. 

 

The first contemporary patches 

Transdermal patches as we know them today began to take shape in the mid-20th century, when skin administration started to be studied in a more structured way. The work of Dale Wurster and his student Sherman Kramer was pivotal in quantifying the passage of substances through the skin. They demonstrated that simple parameters, such as applied dose, contact surface area, skin hydration, and the nature of the backing, directly influence systemic absorption [12]. 

In the late 1960s, Alejandro Zaffaroni patented a transdermal device allowing controlled release of the active ingredient through the skin. This innovation marked a major milestone in the development of modern transdermal systems, as it formalized the principle of prolonged and reproducible drug release [13]. 

During the 1970s, these advances led to the development of the first modern transdermal patches. The first commercially approved transdermal patch by the FDA in 1979 was a scopolamine system intended to prevent motion sickness, marking the beginning of widespread clinical use of this administration route. In the following decades, other approved transdermal systems confirmed the clinical and pharmaceutical value of this galenic form [1], [14]. 

The development of these systems now relies on a balance between the properties of the active ingredient, the choice of adhesive materials, device performance, and pharmaceutical quality requirements. This complexity explains the key role played by specialized industrial partners, capable of supporting development from the initial formulation stages through industrial production. 

Within this framework, AdhexPharma provides expertise in the development of transdermal patches. The company supports the entire process, from galenic design to industrial production, ensuring optimized controlled release of the active ingredient, device stability, and skin adhesion. This approach meets current regulatory and pharmaceutical standards while guaranteeing the safety and efficacy of transdermal systems for patients. 

References

[1]    H. Vimal, « Transdermal devices history, current advances and future prospects », 2023. 

[2]    C. S. Henshilwood et al., « A 100,000-year-old ochre-processing workshop at Blombos Cave, South Africa », Science, vol. 334, no 6053, p. 219‑222, oct. 2011, doi: 10.1126/science.1211535. 

[3]    M. N. Pastore, Y. N. Kalia, M. Horstmann, et M. S. Roberts, « Transdermal patches: history, development and pharmacology », Br. J. Pharmacol., vol. 172, no 9, p. 2179‑2209, 2015, doi: 10.1111/bph.13059. 

[4]    A. (Alfred) Lucas, Ancient Egyptian materials and industries. Mineola, N.Y.: Dover Publications, 1999. 

[5]    D. Lipsker, L. C. Nwabudike, L. C. Parish, et L. J. Hoenig, « Ceratum Galeni: An old eponym honoring Galen and his cold cream », Clin. Dermatol., vol. 41, no 6, p. 735‑737, 2023, doi: 10.1016/j.clindermatol.2023.09.003. 

[6]    V. Picard, « Le Qanûn, la grande encyclopédie médicale d’AVICENNE. », Le Dicopathe. Consulté le: 17 décembre 2025. [En ligne]. Disponible sur : https://www.dicopathe.com/le-qanun-la-grande-encyclopedie-medicale-davicenne/

[7]    H. N. Cole, N. Schreiber, et T. Sollmann, « Mercurial ointments in the treatment of syphilis: their absorption as measured by studies on excretion », Arch. Dermatol. Syphilol., vol. 21, no 3, p. 372‑393, mars 1930, doi: 10.1001/archderm.1930.01440090020002.

[8]    F. D. Malkinson et M. B. Kirschenbaum, « PERCUTANEOUS ABSORPTION OF C14-LABELED TRIAMCINOLONE ACETONIDE », Arch. Dermatol., vol. 88, p. 427‑439, oct. 1963, doi: 10.1001/archderm.1963.01590220059007. 

[9]    M. J. Fox et C. L. Leslie, « Treatment of Raynaud’s diseases with nitroglycerine », Wis. Med. J., vol. 47, no 9, p. 855‑858, sept. 1948. 

[10]    S. H. Gehlbach, W. A. Williams, L. D. Perry, et J. S. Woodall, « Green-tobacco sickness. An illness of tobacco harvesters », JAMA, vol. 229, no 14, p. 1880‑1883, sept. 1974. 

[11]    « Proliferative and other lesions of the male breast. With notes on 2 cases of proliferative mastitis in stilbœstrol workers - Scarff - 1942 - BJS (British Journal of Surgery) - Wiley Online Library ». 

[12]    D. E. Wurster et S. F. Kramer, « Investigation of some factors influencing percutaneous absorption », J. Pharm. Sci., vol. 50, p. 288‑293, avr. 1961, doi: 10.1002/jps.2600500403. 

[13]    « NIHF Inductee Alejandro Zaffaroni Invented Drug Delivery Systems ». Consulté le: 17 décembre 2025. [En ligne]. Disponible sur: https://www.invent.org/inductees/alejandro-zaffaroni

[14]    K. S. Paudel, M. Milewski, C. L. Swadley, N. K. Brogden, P. Ghosh, et A. L. Stinchcomb, « Challenges and opportunities in dermal/transdermal delivery », Ther. Deliv., vol. 1, no 1, p. 109‑131, juill. 2010, doi: 10.4155/tde.10.16.