It is a material so ubiquitous it is often taken for granted. But for the past 60 years, silicone, a synthetic polymer, has had a major impact on the global healthcare industry. It has been seen benefitting patients around the world through a range of applications, from medical devices to active pharmaceutical ingredients (APIs) and excipients in medicines. The material properties and benefits of silicone are well known. They include water repellence and high permeability to gases, as well as stability in extreme temperatures and resistance to chemical and thermal degradation.

“Silicone has unique material properties that make it ideal for certain applications in the biomedical field,” researchers from Northern Arizona University explained in an article previously published in Medical Device Developments. “Its hydrophobic nature, low surface tension, and chemical and thermal stabilitylend to biodurability and generally favourable biocompatibility.”

A brief history

The element was initially discovered by Swedish chemist Jöns Jacob Berzelius in 1824, and first used in the medical sector in the mid-1940s to coat glassware and needles after researchers discovered it could prevent blood from clotting, and shortly after in the fabrication of implants such as bile duct repairs and artificial urethras.

Having demonstrated its biocompatibility, silicone was then supplied on a much wider scale in the 1960s by companies like Dow Corning. By that stage it was being used in a huge variety of healthcare applications such as stents, catheters, drains and shunts, orthopaedics and heart bypass machines.

Today, the market for silicone materials in healthcare continues to grow at an impressive rate, while new material sources and silicone technologies have come to the market offering various performance advantages for medical device manufacturers and patients alike.

According to a 2017 report from Report Buyer, the global market for medical-grade silicone is expected to reach $1.6 billion by 2022, at a compound annual growth rate of 6.1% during 2017–22. By and large, growth is being driven by an increased use of products that use silicone materials, according to Report Buyer.

“Sectors such as implants, dental tools, drug delivery devices, prosthetics, syringes and disposable medical devices fuel the demand growth of medical-grade silicone,” said the report. “Rising demand in the Asia-Pacific region for devices such as surgical implants and a growing elderly population whose medical needs are often met by products fabricated out of medicalgrade silicone is driving growth.”

The long-term effects

Of course, it hasn’t always been plain sailing for silicon manufacturers. In the 1990s, the US Federal Drug Administration (FDA) banned silicone implants following public outcry about alleged links between breast implants and cancer and autoimmune diseases.

However, subsequent studies found no causal links between these factors, however, and in 2006 FDA approved silicone gel-filled implants from two manufacturers with the requirement that they conduct large post-approval studies (LPAS) to monitor its long-term implications.

But the negative attention still had a significant impact on the industry. Companies were forced to make big payouts, including Dow Corning, which filed for Chapter 11 bankruptcy in 1995 after facing 20,000 lawsuits. Subsequently, implantable device innovation in the US slowed, with silicone product development gaining traction in Europe and Asia instead.

However, innovation did continue as the wider medical device market evolved. Increased interest in transdermal drug delivery systems (TDDS), for example, has increased the amount of research and innovation in silicone adhesives, which are used as excipients in the patches.

TDDS is able to eliminate first pass metabolism, where the concentration of a given drug is reduced before reaching the systemic circulation and the pain of hypodermic needles. Silicone based pressure sensitive adhesives (PSA), meanwhile, are known for their skin-friendliness and ability to enhance the efficacy of the drug in transdermal drug delivery patch products

“They offer excellent permeability to lipophilic drugs, and can be further modified by formulating with hydrophilic fillers, copolymers, plasticisers or by modification of the network with silicone-organic copolymers to allow delivery of hydrophilic drugs,” according to a 2015 paper in Future Science by Dow Corning researcher Gerald Schalau.

According to Schalau, patient literature indicates that silicone PSAs, which were first used in TDDS in the 1990 Duragesic fentanyl patch, are now involved in delivering a number of different drugs, including non-steroidal anti-inflammatory drugs, hormones, retinoids and vitamins.

“In most of these cases, silicone PSAs have been noted for enhancing drug delivery in addition to other properties like less skin irritation and sensitisation,” Schalau said.

A number of pharmaceutical formulators are now combining silicone PSAs with other adhesive technologies to create increasingly sophisticated TDDS designs, according to Schalau.

“These have taken the form of layering silicone and other adhesives or other non-adhesive polymers that may act as drug reservoirs, or ratecontrolling layers within the seemingly monolithic TDDS to achieve the desired performance,” he said. “Other unique and advanced patch designs have been created by blending silicone adhesives with non-silicone adhesives and other polymers with differing drug compatibilities to achieve patches with the desired therapeutic release profiles for a number of actives.”

An upward spiral

Silicone materials are considered useful in topical products due to their ability to be retained on the skin over time. According to Schalau, recent research on the antiretroviral HIV drug maraviroc and ibuprofen shows that new silicone elastomer blends can improve drug delivery compared with non-silicone chemistries.

“Use of silicone elastomer gels in a variety of drug delivery applications has been reported via granted or sought intellectual property publications,” said Schalau. “Notable references include formulations or compositions to deliver actives like ingenol angelate, retinoic acid derivatives, amino acids, antiperspirants, clobetasol propionate and several other actives.”

New silicone materials have emerged to support the rapid growth of wearable medical devices, which is driven by an increase in outpatient and home-based care. Medical analysts claim silicone can help promote patient compliance by delivering stable longterm adhesion, as well as breathability and sensitivity to the skin.

“New silicone-based PSAs offer important advantages over acrylic adhesives,” said Christine Weber and Audrey Wipret of Dow Corning in a recent article for Medical Plastics News. “Not only can acrylic adhesives cause skin irritation in some patients, but they tend to increase in peel adhesion over time, making removal of the device uncomfortable. Besides solving these problems, silicone-based PSAs can handle heavier loads than silicone soft skin adhesives, up to several grams, over extended periods. This advanced technology will be an important enabler of next-generation wearable device designs.”

Dow Corning, an industry leader, now offers soft-skin adhesives (SSA) for medical devices that involve shortterm wear and high-adhesive silicones for extended wear-time. The former involves two-part platinum-catalysed, cross-linked silicone elastomeric adhesives that bond quickly to the skin and can be easily repositioned. They are suitable for wearable devices that need to be removed and placed back onto the patient. The latter involves PSAs that offer strong and stable adhesion, and high shear strength without irritating the skin.

Silicone materials used in implantable devices are evolving to cater for a market that is undergoing dramatic transformations due to advancement in the tech industry.

The implants are becoming valuable biomedical control units for monitoring and responding on demand via wireless communication. Devices are getting smaller and are being integrated into electronics which require higher material performance to meet the requirements for integrity and durability.

A recent article by ProMed, the leading medical silicone components and assemblies manufacturing company, offers a number of developments in silicone used for implantable devices. Medical silicone tubing with embedded reinforcements that enhance the natural flexibility of silicone while providing added strength and stiffness have recently hit the market, for example.

“Braided or spiral monofilaments of stiffer resins, or even stainless steel, are located in the wall of the tubing and providing enhanced burst, kink and wear resistance – all qualities necessary for tubing which needs to conform around organs and through existing passageways as it is inserted into the body,” said the ProMed article.

“This new development can meet the current pressing need for more durable and smaller implantable medical devices.”

In most cases, silicone PSAs have been noted for enhancing drug delivery in addition to other properties.
– Gerald Schalau, Dow Corning

A softer approach

Soft silicone materials are being used to 3D print implantable devices according to ProMed. While this has so far only been achieved inside a university laboratory, it could eventually help reduce the cost of time-consuming, conventionally moulded implants that are custom made for individual patients.

“The breakthrough in this case is the ability to 3D print parts by using oil-based microgels, a welcome achievement since that material’s flexibility and pliability makes it ideal for implants that are located in and around delicate internal organs,” said the article. “Although this technology is at an early stage in the development process, it does demonstrate how medical-grade silicone continues to be at the forefront of new implantable devices.”

While silicone materials have proved safety credentials, appropriate manufacturing practices remain crucial for further innovation.

“Manufacturing practices must strictly adhere to regulatory requirements and industry standards,” said the researchers and consultants writing for this magazine. “Decisions regarding the sourcing of silicone material should conform to manufacturing and regulatory requirements.”

In sourcing the right material, Medical Device Developments suggests pharmaceutical companies should ask a number of key questions, such as how long will the device reside in the human body? What FDA regulations will apply? What testing is available from the raw material supplier? What testing must be performed by the device manufacturer itself, and how long will the testing take?

While these questions might sound tedious, asking them will enable medical device companies to make sure they are using silicone to its full benefit – something decades of use and innovation will tell you is worthwhile doing.