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CBD Patches – How Do They Work? The History of Transdermal Drug Delivery (TDD) Systems

Posted by Lewis Olden on
CBD Patches – How Do They Work? The History of Transdermal Drug Delivery (TDD) Systems

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Transdermal Patches, such as CBD patches, are currently widely used as a cosmetic, topical and transdermal delivery system. Transdermal patches represent a key by-product of the growth and improvement in skin science, technology and expertise acquired through trial and error. Clinical observation and evidence-based therapies are also integral on developing effective transdermal patches.

The skin is the largest organ in the human body with a surface area of between 1.5 and 2msq in fully grown adults. Medications have been applied to the skin to treat an array of conditions in the medium of transdermal administration of therapeutics to manage systemic ailments. Cosmetics have been applied to the skin since medical records began. The use of ointments, potions, salves and even patches containing of plant, mineral or animal extract were popular in ancient Egypt and in Babylonian medicine (3000 BC). However, the use of transdermal delivery methods only become common practice towards the end of the 20th century. This was due to advances in technology to enable precise and reproducible administration through the skin for systemic effects.

History of Topical Therapy

Topical remedies applied to the skin are believed to have been used since the origin of mankind.

The ancient Egyptians used olive oil and sesame oil in combination of animal’s fats to make their cosmetic and dermatological products. The Egyptians also formulated perfumes using almond, rosemary and peppermint. The mineral ores of lead and copper were used to create kohl which was a paste that the Egyptians used to paint their eyes. Red ochre was a lip or face paint and a mixture of powdered lime and oils were used as a cleansing cream.

These topical products were used for both aesthetic purposes and for protection against eye diseases, this was due to a religious belief that was widely held at the time. It is actually believed that these effects were genuine, as recent studies that involved the incubation of low lead ion concentration with skin cells produced NO which is believed to provide defence against infection.

A Greek physician named Galen introduced the compounding of herbal drugs into dosage forms. Galen is often considered to be the ‘Father of Pharmacy’ and his teachings are known as the ‘Galenic Pharmacy’. Galen’s Cerate, which is a cold cream, is probably his most famous formula and the composition remains pretty consistent to this day.

Medicated plasters were applied to the skin in Ancient China and were the early predecessors of today’s transdermal patches. The early plasters contained multiple ingredients of herbal drugs dispersed into an adhesive made from natural gum rubber base which was the applied to a backing support made from a form of paper.

Nicotine, commonly thought of as a modern transdermal agent was used in a plaster during the time of Paracelus (1493 – 1541). The Western style of plaster were far simpler as they only included one ingredient, whereas the patches formulated in China often contained multiple ingredients.

At the beginning of the 20th century, it was understood that the skin was relatively permeable to lipid-soluble substances but not to water and electrolytes.

Various in vivo studies illustrated systemic absorption after topical application by estimating the drug levels in blood and urine.

The first report of clinically managing a systemic condition through topical application was probably the work of Zondek in the 1950s. Zondek reported that chloroxylenol which is an external disinfectant which is still used in soaps today, could be an effective treatment for urogenital infections when a 30% lanolin ointment was applied. 

The development of adhesive transdermal delivery methods was a key factor in reaching the quality of transdermal patches available on the market in this modern age.

There are both first and second generation transdermal drug delivery systems. Both have been proved to be effective in their own right, it is fascinating how science evolves over time.

First Generation Transdermal Drug Delivery (TDD) 

Delivering drugs using transdermal methods is advantageous over oral and many conventional methods. Transdermal delivery ensures that the absorption of the drug is controlled resulting in more uniformed plasma drug concentrations. The bioavailability of transdermal delivery systems such as patches are improved because they avoid first pass hepatic metabolism and pH associated deactivation. 

The first generation of transdermal drug delivery is the method behind the majority of transdermal patches that have been used in medicine and been approved for clinical use. The nicotine patch helped smoking cessation a lot by suppressing a smoker’s craving for a cigarette.

Second Generation Transdermal Drug Delivery (TDD)

The second generation of transdermal drug delivery works with advanced understanding of the permeability of the skin. Skin permeability enhancement is needed to expand the scope of transdermal delivery. Most transdermal products that have been commercialised have used iontophoresis, this is an advanced method of transferring the drug being administered across the skin using an electrical potential difference.

The forthcoming transdermal drug delivery technology is likely to use microneedles as a method of circumventing the stratum corneum which will enable more disruption of the stratum corneum barrier, ultimately leading to a more effective method of delivery the CBD.

Variations of Transdermal Patches  

There are three variations of CBD and transdermal patches, Reservoir, Matrix and patches with an active adhesive. 

Reservoir Patches

The varied dosing and possible transfer of the active ingredient within ointments and creams emphasises the need to have a controlled and safer delivery systems. This was a major driver in the research and development into more sophisticated delivery methods like transdermal patches. The first one of these systems was a combination of a rate-controlling membrane and a reservoir containing the active ingredient. This was invented by Alejandro Zaffaroni via his company named Alza. The first commercialised patch was a scopolamine transdermal patch.

The crucial belief behind this first transdermal patch was that it was the device and not the skin that controlled the delivery of the drug into the bloodstream. The first transdermal patch was formulated to minimise motion sickness. The precisely controlled delivery system administered the drug into the bloodstream through the skin which had an adequate therapeutic effect. It also minimised the undesired adverse effects on the central nervous system, such as drowsiness and confusion. A patent was filed in 1971 which described a patch that used this concept. This was quite revolutionary when compared to other transdermal patches of the time.

Reservoir patches have a reservoir of the drug that is to be administered and the drug is transferred from this reservoir through to the skin.

Matrix Patches

When matrix patches were first developed, they became the dominant method of delivery in the transdermal patch market. Matrix patches became the preferred method because they were thinner, more flexible and more comfortable to wear for the user. Matrix patches are also less expensive than reservoir patches to manufacture.

All patches that don’t contain a liquid reservoir may be regarded as a matrix patch and these patches can be applied to the skin by either gluing the back to the skin adjacent to the matrix or an adhesive on the matrix to the skin. When a substance is suspended in an internal matrix in the packet or in the adhesive itself of the patch without a distinct internal reservoir, the delivery can be steady. Matrix patches can deliver at a constant rate over a multiple day course because as the drug is released from the patch and absorbed the substance dissolves back in the adhesive and compensates for that which is released.

Active Adhesive Patches

Active adhesive/DIA patches simply incorporate the drug being administered entirely in the pressure sensitive adhesive (PSA). The design is in principle still a matrix patch. These patches are state of the art transdermal patch design. The active drug is directly included in the adhesive polymer and this not only fulfils the adhesive function, but it also controls the delivery rate of the drug.

Active adhesive patches are easy to make once you have figured out the formulation. Formulating an effective active adhesive transdermal patch is extremely challenging and this is why it is so difficult to find an effective transdermal patch.

CBD Transdermal Patches

CBD is one of over one hundred cannabinoids within the cannabis plant. CBD has no psychoactive effects and can help the user in many ways. THC is the cannabinoid that causes the user to get ‘high’ and it is currently illegal in the UK.

CBD has been proven to have anti-inflammatory, pain relieving, sleep inducing and anti-anxiety effects and properties. 

CBD patches are a fantastic way to consume CBD. Many people do not like the taste of CBD so CBD patches are a great way to avoid this. CBD patches can provide 24-hour relief and can allow the user to only have to use CBD once a day to get relief throughout the entire day.

The Future of Transdermal Drug Delivery (TDD) Systems

The future is of transdermal patches will be an interesting journey. Transdermal patches are coming to market on an increasingly frequent basis. The hottest issues in the transdermal patch space at the moment is microneedles and other innovations that remove the stratum corneum. However, there is yet to be an approved product that uses microneedles. There have been many patents filed for such delivery methods. The is increasing clinical evidence to support the efficacy and safety of such patches. There is a worry that patients and users may not be comfortable with the idea of microneedles though. 


Topical delivery systems have been used for numerous ailments and cosmetics have been used since the dawn of man. Throughout the years there have been many different drugs that have been candidates for transdermal delivery. Various changes in drug dosing and other factors have led to constant innovation within the transdermal patch space.

A key focus in the transdermal patch space is discovering what drugs are best suited to transdermal delivery. CBD and other cannabinoids such as THC could be ideal candidates as CBD patches seem to be extremely effective delivery method for administering CBD.

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