Transdermal medicines have several immediate benefits. First, a transdermal patch applied to the surface of the skin provides sustained drug delivery over a prolonged period. It also helps reduce the risk of toxicity, thanks to the slow-release mechanism of action, and it avoids the issues long associated with the first-pass effect of orally administered medications.

But, transdermal technology isn\’t perfect. As one review in the Frontiers in Bioengineering and Biotechnology accurately described, the skin is a very \”effective barrier.\” As the body\’s largest organ, its primary role is to protect the inside from the outside. The skin\’s job is to keep the elements out, like harmful bacteria, viruses, and other pathogens. 

Circumventing these natural characteristics to deliver therapeutic compounds is one of the biggest challenges researchers face for improving transdermal medicines.

Heat in Transdermal Medicine

A 2017 paper, published in Expert Opinion on Drug Delivery, suggested heat as a possible design feature to improve transdermal drug delivery and effectiveness. Through exposure to higher-than-normal temperatures, drugs may become more or less transpermiable.

The body responds to increased temperatures by focusing on increasing skin blood flow. This is the body\’s attempt to return temperatures back to normal, like internal air conditioning. But, increased blood flow works to improve absorption rates for transdermally applied medicines.

In some cases, controlled heat could help improve a drug\’s effectiveness by improving its ability to move through the skin and into the bloodstream. But, in other cases, this could prove dangerous, especially for drugs with higher risk profiles, like fentanyl and other opioids.

As the authors of the above paper summarize, there have already been several studies exploring how specific compounds, including fentanyl, testosterone, and nicotine, react to increased temperatures.

Increased Blood Flow Could Increase Effectiveness, With Caveats

In the 2017 paper, the summarized evidence tells us that heat increases skin blood flow, which subsequently increases drug absorption and plasma drug concentrations. 

Though, in most cases, we don\’t yet know how cannabinoids and other novel plant-based formulas could react under these conditions, an earlier study has explored transdermal nicotine. In a controlled setting, researchers increased the temperature applied to a transdermal nicotine-containing application from 32°C to 43°C. As a result, they measured a 10-fold increase in blood flow and, remarkably, \”up to 13-fold increase in nicotine uptake.\”

While cannabinoid studies lag, work with other compounds (like those mentioned above), evidence strongly suggests that locally applied heat could very well increase the therapeutic potential of topicals.

It could apply to other plant-based therapies as well, including psilocybin, a theory which Ei.Ventures plans to explore in the near future. Read more about the Letter of Intent between RYAH and Ei.Ventures to Develop New Delivery Solutions for Psychedelic Research here.

The key, it seems, is to ensure heat is used in a controlled manner and only with approved formulations. There are plenty of warnings and even a few documented case studies detailing the risks of combining fentanyl patches with excessive heat. Whether from excessive outdoor physical activity, an electric blanket, or even a sauna session, some substances like fentanyl are not suitable for heated transdermal application.

So long as the patient and/or device has control over the temperature and knows the specific recommendations for each formulation, transdermal therapies have an incredible potential for a wide variety of applications.

Additional Considerations for Skin-based Delivery Systems

Throughout the development process for the RYAH Smart Patch, several other considerations beyond heat have made their way into the design. 

The first is the viscosity and molecular size of the formula. Cannabinoids, in particular, pose significant challenges for topical applications because the molecular size of THC or CBD is dramatically larger than the average pore size. As one report detailed, the average CBD molecule is roughly 4000 nanometers (nm) in size, but for complete absorption through the dermis, the molecule must be under 80 nm.

Cannabinoid nanoemulsions are one option. This preparation breaks apart large molecules into smaller pieces, suitable for deeper penetration. Another option, once again, is heat. The Smart Patch specifically incorporates gentle heating elements into the Patch Brain, which could help open pores and improve absorption rates.

The Smart Patch also offers several variations to the permeability of the medical cotton release liner, which is the barrier between the plant-based formula and the skin\’s surface. Different liners would allow for fast release, slow release, or even a no-release until Boosted option.

Altogether, these design features, including the formula viscosity, controlled temperature Boosts, and liner permeability, create a precision delivery system. What\’s more, its highly customizable to each formula and application. As a result, its a smart device offering unprecedented control for the delivery of a wide range of formulas.