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Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.
Transdermal patch design, materials, and manufacturing variables, as well as drug formulation and interactions between the API and the adhesive, can affect adhesion and drug delivery.
Transdermal patches deliver drug through the skin and can be designed for extended release from hours to several days. Pharmaceutical Technology spoke with Gene McNamara, Research Specialist at 3M Drug Delivery Systems, about some of the considerations for developing and manufacturing transdermal patches.
PharmTech: What are some of the primary considerations for developing and manufacturing patches?
McNamara(3M): Transdermal patches are a non-invasive way of self-administering medication. Because the drug is delivered through the skin, it avoids the gastrointestinal tract, so there are potentially fewer side-effects. Patches offer the ability to maintain a constant therapeutic effect for up to seven days. Transdermal patches also allow for removal of a drug in the event of an adverse reaction.
Not all medications are the right fit [for delivery using a patch]. In order to achieve proper skin absorption and penetration, the API should be non-ionic and be relatively lipophilic to enable partitioning into the lipophilic skin barrier. The molecular weight should be under 500 Dalton, as larger molecules cannot pass through the stratum corneum. The therapeutic dose of the drug should also be less than about 10 mg per day. Finally, FDA has strict standards on elemental impurities in drug substances and delivery methods that must be considered.
When it comes to pairing a drug with a patch, there are many things to consider. What is the release rate of the drug? Does it need to be administered over the course of a few hours, a day, or a week? When the API and adhesive are mixed together, it can speed up the rate at which the drug passes through the skin (because the drug is closer in proximity to the skin), but it can lessen the effectiveness of the adhesive itself. In some cases, the API and adhesive cannot be mixed together, because their material components are simply not compatible, thus requiring an alternative layering structure within the patch.
When it comes to manufacturing controlled substances, there are significant challenges to consider, including regulatory hurdles, supply chain issues, and safety and security concerns. It is important to maintain strict checks and balances in order to properly follow policies and procedures.
We have developed four options for the construction of a patch to ensure the optimized delivery of any given drug based on varying factors, such as the prescribed release rate of the drug and how long the patch must stick to the skin. The differences between these options boil down to how the liners, membranes, backings, and overlay tapes are all layered together. In two of those layering options, the drug is mixed with the adhesive (known as drug-in adhesive), and in the other two layering options, the drug is in a separate layer of its own.
PharmTech:What variables affect adhesion of the patch to the skin?
McNamara(3M): Patient skin is the single biggest variable. Everyone has different levels of tolerance and sensitivity to adhesive materials. We run tests to the extent that we can, but until someone tries a patch for the first time, there is no way to know how his/her skin will react to it.
Beyond that, anything that you put into an adhesive can have an adverse effect on adhesion. If the drug and the adhesive are mixed together, the strength of adhesive may be diminished. Conversely, if the drug is not combined with the adhesive, and instead placed into a different layer of the patch, the adhesive will stick to the skin for a longer period of time.
On the manufacturing side, there are a number of things that can affect adhesion. For instance, to maintain high adhesion, the material can’t be too thick or too thin. The processes for laminating and drying the product also play a role.
There are ways to assist adhesion. If a patch itself is not strong enough to stick for the prescribed length of time, overlay tape can be used to help keep it in place. Medical tape can provide for a longer wear period, without affecting the drug delivery. So, when a longer lasting patch is necessary, we incorporate overlay tape into the design of a patch.
PharmTech: What trends do you see in use or manufacturing of transdermal patches?
McNamara(3M): The switch from new patch formulations to generics continues to be a trend that is impacting many aspects of our industry. Most of the major categories of transdermal drugs in the United States have generic forms, and there are now also over-the-counter options competing for consumer dollars. With that trend comes the growing need for increased speed and flexibility in order to compete in a fiercely competitive space.
In the generics world, a successful business model is dictated by three main factors: being the first to arrive on the market, offering the lowest cost option for consumers, and maintaining the quality expected from the brand-name product. Manufacturers of transdermal patches are facing significant price pressure. They must produce a high-value product at a low cost.
We know this reality creates major pain points for everyone in this industry. At 3M Drug Delivery Systems, we’ve recently made significant investments in new high-efficiency transdermal manufacturing equipment to make the process more efficient. Under current market pressures and time constraints, it is more important than ever to prevent malfunctions of equipment and materials, so quality is key. Using lower-cost/lower-quality materials may seem like a smart move, but in fact, it poses a substantial risk.
Vol. 42, No. 12
When referring to this article, please cite it as J. Markarian, "Developing and Manufacturing Transdermal Patches," Pharmaceutical Technology 42 (12) 2018.