Entering into the transdermal medication market is no easy task. It’s a market segment heavy in regulations, tight on tolerances, and requires precision equipment. While the profit margins can be substantial, it will require a major investment in resources and talent.
If you’re a converter looking to enter the transdermal medication market, one of the most important considerations is choosing the right transdermal patch materials. We sat down with 3M’s Material Support Representative Charlene Schubert to provide insight on this selection process.
What is a Transdermal Patch?
A transdermal patch is used to deliver medication through the skin. An adhesive patch containing medication is placed onto the skin, and a specified dose is then absorbed through the skin and into the bloodstream.
For patients and caregivers, it’s a non-invasive, painless way to administer medication that provides a constant therapeutic dosage for a limited period of time.
Before we delve into how to choose the right materials for a transdermal patch, let’s break down its key components and design. 3M has produced the following video with the breakdown, which we’ve transcribed below.
Parts of a Transdermal Patch
Backing – The outermost layer of the patch, which protects the formulation during the wear period.
Drug – The drug contained within the membrane or in the adhesive.
Membrane – The film that controls the rate of drug diffusion out of the patch, to the skin.
Adhesive – The skin contacting layer that adheres the patch to the skin.
Overlaminate Tape – The external protective covering or functional layer which can be directly integrated into the patch design.
Release Liner – Protects the skin-contacting adhesive during storage and is removed prior to application of the patch.
Step #1 – Consider the Drug Properties
The transdermal patch design is dictated by the properties of the drug. If you’re working with an active ingredient, you’ve likely already characterized it. These are typically the main areas considered:
Molecular weight: The size of the drug molecule – only small molecules can penetrate the skin – typically less than 500 Daltons.
Lipophilicity: The lipophilicity of the drug will determine how readily the drug is absorbed into the body’s oils.
Dosage form: In what form will the drug be administered?
Salt: The drug’s salt form also determines how quickly it can be absorbed into the skin.
Length of time worn: The dosage will depend on the duration of time the patch will be worn. Administering 3 mg versus 10 mg is a big difference. You have to be reasonable as to how much drug you can get into the patch, and how long it can realistically be worn.
Melting point of the active ingredient: Not only must the active ingredient in the drug be suitable to skin, but it can’t be at a level where it prohibits the actual manufacture of the patch itself.
Step #2 – Choose a Transdermal Patch Design
Transdermal patches are typically designed in four ways. The properties of the drug, the dosage level, and the time required to administer the drug typically influence which of these designs you choose:
1. Matrix – Blends an active ingredient directly into the patch. This is the most common method, which is frequently known as the drug-in adhesive, or DIA.
2. Classic Reservoir – Encases an island of active ingredient. Typically a blister pouch with rate-controlling membrane on one side and impervious backing on the other.
3. Polymer Reservoir – Semi-solid drug containing polymer matrix, in direct contact with the skin, with an adhesive ring around the matrix to adhere to the skin.
4. Multilaminate Solid-State Reservoir – Delivers two drugs at different release times. Commonly uses a bolus dose to begin, and follows with a maintenance dose.
We can drill down further into variations of these four overall designs, but these typically comprise the starting point. The approach you choose will be based on the specifications of the drug and the dosage.
Step #3 – Selecting the Materials and the Equipment
The next step is choosing the right materials. This includes the liner, backing, membrane, overlaminate tapes — all of which must be balanced with the drug properties and the chosen design.
The production equipment also factors into the material consideration. If a patch manufacturer has materials that require processing under low tension, they must also have the right transdermal patch manufacturing equipment on hand.
“Compatibility between materials and equipment is essential for a smooth commercialization process,” Schubert notes. For example, if a component roll is 48” wide, it is better to run 12” rolls with no waste versus cutting materials into two (2) 17” rolls with a yield loss of 14”.
The Transdermal Intangibles: Other Important Considerations
We’ve touched on a number of big-picture issues for you to ponder, but Schubert highlighted a number of other important areas of note to transdermal newcomers:
Check for a Drug Master File
As you’re reviewing material vendors, make sure they have a Drug Master File (DMF) established with the FDA. The Drug Master File is a confidential document provided from a material supplier to the FDA. It provides details on how a product is manufactured.
When you’re producing a new transdermal product, you submit a request to the FDA, who then accesses the DMF and makes a ruling on whether or not the product is approved.
Know Your Volumes
Part of the design process above includes knowing the volumes you will be targeting. That can dictate the type of equipment to purchase and the materials you’ll use.
Keep Updated on FDA Guidelines
Whether it’s your company or the vendors you’re working with, make sure a close eye is kept on the evolving FDA guidelines. As Schubert pointed out, they will not only dictate much of your design, but they can also lead to innovation.
For example, at one point, the FDA was interested in patients’ abilities to clearly identify the difference between the liner and the patch itself. Regulations were being considered that would require differentiation between the patch and the liner. For example the patch would be opaque and the liner translucent.
Opaque, writable backings also allow patients and providers to record the date the patch was applied.
Even though the FDA did not enact the proposed regulations, 3M reacted to them and produced an innovative new backing. It’s a perfect example of how embracing and understanding the intent of regulation can lead to positive innovation.
Work With Materials and Machine Vendors Throughout the Process
The entire transdermal patch development process is remarkably complicated and subject to multiple variables. But it’s not an untamable beast.
The key is to align yourself with partners who understand the product, the process and its complexities. You have a long road ahead of you. Take the time to understand who has travelled down that path before to better ensure the trip is successful.
As with all transdermal patch components, however, it is the customer’s sole responsibility to determine the suitability of patch components for the intended use of their product and to ensure the necessary safety and toxicity standards are met.