When science and nature combine in just the right amounts, the results can be astounding. Take transdermal drug delivery, which is expected to grow substantially in the next decade, with microneedle-based delivery devices expected to reach annual sales of 485 million units by 2030, according to research published by Roots Analysis Private Ltd., Microneedles for Transdermal and Intradermal Drug Delivery, 2014-2030.

Fig. 1 – Transdermal patches provide an excellent option for effective drug delivery, reaching the body more systemically than hypodermic injection.

That figure is no surprise to those involved with transdermal drug delivery, which is one of those perfect blends of technology and medicine. The benefits of transdermal delivery over other methods are numerous—it provides a vastly superior experience for the patient in a large number of cases.

One reason for the expected market growth is advances in microneedle technology, including the use of liquid silicone rubber (LSR), which provides smaller, stronger polymers that are more stable and, thus, last longer through more uses. Details on engineering and manufacturing advances are outlined later in this article.

Microneedles Solve Longstanding Medical Challenges

There are several types of transdermal devices, including patches that are placed on the skin, allowing medication to be absorbed through the skin into the bloodstream, and implants, which create a port through which medicine can be delivered. (See Figure 1)

Essentially, transdermal delivery is any drug administration that involves active ingredients being delivered across the skin for systemic distribution.

Perhaps the most promising devices being introduced today are those involving microneedles, which are divided into four types.

Hollow: These infuse a drug through the bores with adequate flow.

Solid: These puncture holes in the skin to increase permeability where a drug can then be delivered.

Coated: These are coated with a drugcontaining dispersion.

Polymer: These are made from special polymers that offer dissolving, non-dissolving, or hydrogel-forming options.

Transdermal devices using microneedles solve a long-standing medical problem: the skin’s anatomical peculiarities make it difficult to cross. The skin’s major barrier consists of the stratum corneum, the outermost layer. However, the layer underneath, the viable epidermis, also plays a protective role. According to research from Touro University published in the journal, Pharmaceutics, only compounds that are able to get through the stratum corneum and diffuse through both layers of the epidermis have the potential to reach circulation and achieve systemic effects.

Benefits of Transdermal Drug Delivery

One obvious benefit of transdermal microneedle delivery is that it reduces the need for hypodermic injections. Although they’re effective, hypodermic needles can cause discomfort, bruising, and even hypersensitivity at the injection site. For patients receiving an occasional vaccine, this is a minor inconvenience. The effects are much more serious for patients requiring daily or weekly injections. A transdermal patch is virtually pain free and can be self-administered, resulting in improved medication compliance, according to research published in the journal, Respiratory Medicine.

Fig. 2 – LSR technology allows the fabrication of unique shapes and smaller sizes. It works well for microneedle patches because it does not cause skin irritation.

Another benefit is improved drug delivery, especially over an extended period. Orally-administered drugs must travel through the metabolic system of the liver, which eliminates a substantial amount before widespread distribution. Less drug is needed when administered through a transdermal device. In addition, a transdermal patch can deliver an even flow of the active ingredient over an extended period, ranging from 24 hours to 7 days.

Many oral medications do not absorb well in the gastrointestinal tract, resulting in low bioavailability. The bioavailability of a patch is also fairly low, but placed correctly, it can avoid first-pass metabolism and partial elimination.

Microneedle patches also permit site-specific dosing. For example, placing the patch on or near an injured appendage can reduce inflammation locally, rather than having the drug circulate throughout the entire body. Studies have shown that changes in the absorption and distribution of drugs administered via patches are quite different from those take orally.

Patches provide a different way to control a drug’s pharmacokinetics. Taking a pill once a day is relatively easy to remember. However, to reduce side effects or offset a metabolism issue, patients sometimes need to take a pill multiple times a day at precise intervals. This is inconvenient for patients and especially difficult to manage overnight. Patches allow for exact control of both dose and time. Twice the size of a patch means twice the dosage. When you need to stop dosing, you remove the patch.

Finally, there is evidence that transdermal microneedle methods are more effective than hypodermics for immunization. Certain cells in the epidermis and dermis (Langerhans and dermal dendritic, respectively) are part of the skin’s unique immune system. Because these cells are designed to initiate immune responses to protect the body, less vaccine is needed to initiate a defense response when administered via a transdermal patch than intramuscularly.

Microneedle Development and Manufacturing

Large strides have been made in recent years in the design and manufacturing of microneedles, in part due to materials advances. Specifically, silicone has become an excellent materials option because of its haptic properties. In addition, silicone does not cause skin irritation, is biocompatible, and is compliant with medical industry regulations.

Liquid Silicone Rubber (LSR) technology has proven particularly suitable for transdermal drug delivery, providing small, strong polymers that are stable and long wearing. Microfabrication of needles requires the incorporation of parts weighed in micrograms or nanograms, and LSR allows complex, high-precision components to be produced in large volumes in these dimensions with relative ease and precise accuracy. (See Figure 2)

Keep in mind that transdermal administration is not appropriate for all types of drugs. The optimal physicochemical properties of the drug and its biological properties must be considered, along with the pharmacokinetic and pharmacodynamic properties of the drug. The most important requirement is the need for controlled delivery, such as short half-life, adverse effect associated with another route, or a complex oral or IV dose regime.