Liquid Silicone Rubber vs High Consistency Rubber for Medical Device Components

Silicone elastomers have long been a popular material for medical devices and medical device components due to their durability, ease of molding by many methods, wide temperature range, chemical inertness, high tensile strength, vast range of available durometers, low toxicity, and compatibility with many sterilization methods. Furthermore, silicone is compatible with human tissue and body fluids, has a very low tissue response when implanted, and does not support bacteria growth – making it a perfect option for implants due to its excellent biocompatibility.

Silicone elastomers are available in two commercial forms: Liquid Silicone Rubber (LSR) and High Consistency Rubber (HCR). HCR is known for its gummy consistency and mostly comes in partially vulcanized sheets. LSR is a newer technology and starts out as a 2-part liquid that cures into a solid form when mixed. LSR generally comes in buckets and has a longer shelf life than HCR.

Medical device OEMs often face a tough decision: should we use HCR or LSR for our medical device component manufacturing? LSR and HCR are both used to manufacture medical device products; however, there are some key differences. The following compares LSR and HCR to shed some light on their differences and when each should be utilized.

Viscosity Difference Leads to Different LSR and HCR Manufacturing Techniques

The performance characteristics of HCR and LSR are relatively similar; however, viscosity is a key differentiator between LSR and HCR, and has a significant impact on the equipment and processes used to manufacture each of these elastomers.

Simply put, viscosity is a measure of a material’s ability to flow. A low viscosity indicates a material is less viscous and more readily flows where a high viscosity indicates a material is more viscous and less apt to flow well. For reference, water has a relatively low viscosity and easily flows whereas molasses has a higher viscosity and is more resistant to flow.

LSR has a lower viscosity than HCR. Due to the lower viscosity, LSR is most often processed via injection molding. LSR’s desirable handling properties and lower shrink rate make it an excellent choice for manufacturing highly complex geometries and intricate products. Additionally, due to the automated nature of injection molding, LSR can produce high volumes of components in a short period of time. For this reason, deciding whether HCR or LSR injection molding is the better choice for your project largely depends on the production volume required.

A lower viscosity makes it easier for manufacturers to mix additives into LSR. Additives that can readily be incorporated into a batch of LSR include colorants, desiccants, barium, and pharmaceuticals such as hormones or steroids. For these reasons, LSR is a great option for medical devices such as combination products. The low viscosity of LSR and the temperatures needed to vulcanize LSR are usually low enough that significant degradation of compounded substances, like Active Pharmaceutical Ingredients (APIs) that are used in combination products, can be avoided.

Due to its higher viscosity and more challenging handling properties, HCR is typically processed using compression and transfer molding methods, which are more labor-intensive. In some cases, HCR is used in injection molding projects.

OEMs Often Prefer LSR

For companies already using HCR to manufacture medical device components, it may make sense to continue using this elastomer especially since the initial capital equipment costs have already been made. For new product development, however, LSR is often the best choice given the lower capital costs and labor associated with processing this elastomer. Due to its lower manufacturing cost and versatility with formulations, companies often prefer LSR over HCR – but the decision is on a case-by-case basis.

ProMed’s Silicone Manufacturing Capabilities

At ProMed, we combine industry-leading medical-grade LSR and HCR expertise with the latest developments in silicone materials and technology. We have garnered a reputation as the world benchmark of implantable silicone components and assemblies. From helping OEMs incorporate the latest medical-grade silicone formulations into their designs to delivering rapid silicone prototypes, we serve as a premier silicone molding contract manufacturer for medical device OEMs.

ProMed has expertise in working with the full spectrum of silicones covering a wide range of properties and characteristics. Our wide range of materials include: Liquid Silicone Rubber (LSR) 5 to 80 Durometer, High-consistency Rubber (HCR): 20 to 80 Durometer, Room Temperature Vulcanizing silicone (RTV). We will assist in your material selection to help ensure all design requirements are met.

Our manufacturing facilities and equipment are designed for a single purpose—to mold medical and implantable silicone, combination components, and bio-material grade plastics with uncompromising quality and service. We currently have four divisions that are located within two manufacturing sites. All are certified class 10,000 / ISO Class 7 cleanrooms.

Contact ProMed today at 763-331-3800 to discuss your next medical device project.


drug eluting

Implantable Drug Delivery Devices - An Overview

Introduction

Implantable devices are called upon to serve a variety of functions, from vascular stents that preserve blood flow to electrostimulation devices that regulate heart rhythm or block spurious signals in the brain, to orthopedic devices that mechanically reinforce the spine or restore range of motion of hips and knees. For over a decade there has been an increasing convergence between implantable devices and drug therapies, including devices that deliver drugs as a primary of action. This article reviews some representative applications that materials and processes device designers can leverage in developing new products for these growing markets.

Why implantable devices for drug delivery?

Implantable drug delivery devices offer several advantages over conventional oral or parenteral dosage forms. First, implantable devices allow site specific drug administration where the drug is most needed. Examples include implants used in the treatment of brain tumors (Gliadel® wafer) or prostate cancer (Lupron® depot). This may also allow for significantly lower doses of drug which can minimize potential side effects. Second, implantable devices allow for sustained release of a therapeutic agent, as highlighted in the accompanying illustration (Figure 1). The last and perhaps most important advantage is patient compliance, as the treatment regimen associated with an implantable device is generally less burdensome than pills or injections.

Figure 1: Idealized comparison of tissue drug levels for injections compared with an implantable drug delivery device. Clearance of the drug after an injection may result in significant time outside of the therapeutic window.

Types of drug delivery devices

Implantable drug pumps are used to deliver insulin in the treatment of diabetics and to administer pain medications directly to the spine (intrathecal pumps). These are typically programmable “active” devices which require regular resupply of the medication through an access port. Subcutaneous solid implants, conversely, provide long-term, “passive” release without the need for replenishment. Typically found as thin flexible rods or “matchsticks”, these delivery systems are particularly effective for the delivery of highly potent drugs such as hormones. Commercial examples include histrelin implants for the palliative treatment of prostate cancer and uterine fibroids(Vantas®), and early puberty in children(Supprelin®), levonorgestrel (Jadelle®) and etonogestrel (Implanon®) implants for family planning, and buprenorphine for the treatment of opioid addiction (pending FDA approval). Additional indications in development include subcutaneous implants for treatment of schizophrenia, breast cancer, photosensitivity, and Parkinson’s disease.

A number of promising solid implant applications can be found in ophthalmology for the treatment of macular edema and retinal vein occlusion using corticosteroids (Osurdex®), with products in development for the treatment of glaucoma (prostaglandins) and age-related macular degeneration (anti-VEGF).

Opportunities in women’s health

In addition to subcutaneous implants, novel drug delivery forms such as intrauterine devices (IUDs) and intravaginal rings (IVRs) and are finding increasing applications in the area of women’s health. For more than two decades after serious safety issues were encountered with the Dalkon shield, no IUDs were marketed in the US. In 2000 the FDA approved a levonorgestrel eluting IUD (Mirena®) providing contraception for up to 5 years of use. Later, use of the device was expanded to include an indication for severe menstrual bleeding and a smaller device (Skyla®) has been approved for women who have not had children. IVRs are commercially available for contraception (Nuvaring®), hormone replacement therapy (Estring®), and to improve the rate of in vitro fertilization (in development).

Contraceptive devices used made from silicone (IUD, left) or ethylene vinyl acetate (IVR, right)

Materials for drug delivery

As with all implantable devices, key materials considerations for use in drug delivery include biocompatibility, stability and durability (except in the case of biodegradable drug delivery systems), and the ability of the material to control release of the active pharmaceutical ingredient (API). Silicones have long been a material of choice for drug delivery given their extreme chemical inertness, range of stable mechanical properties, and ability to compound various APIs within the matrix. The rate of release is generally proportional to the loading of drug within the silicone, typically 5-50% by weight. Ethylene vinyl acetate (EVA) is also finding use in drug delivery application due to the additional ability to control release rate by varying the vinyl acetate content. Like silicone, EVA is processed at relatively low temperatures, typically 150-250oF, which helps to minimize risks associated with degradation of the API. Polyurethanes and acrylate hydrogels have also been utilized in select applications.

Another option is to use a biodegradable material such as poly(lactic-co-glycolic acid) or PLGA to controllable release the drug while essentially “dissolving away” by hydrolysis to produce lactic and glycolic acid. While clearly most developers exhibit a preference for materials with an established history of use in vivo, new materials for drug delivery remain an active field of research, including tyrosine-derived polycarbonates which have the added benefit of being inherently radiopaque.

Processing of drug delivery materials

All of the above materials lend themselves to manufacturing processes based on molding or extrusion. At ProMed, work has historically focused on molding silicone drug delivery devices using injection and compression molding techniques. Several factors must be considered in optimizing the material formulation and developing a robust molding or extrusion process. The material system (e.g. liquid silicone vs. high consistency rubber), mixing or compounding technique, API particulate size cure temperature, and pressure will all potentially affect the drug release consistency and drug content uniformity of a manufacturing lot. In some cases, co-extrusion or over molding of a thin, drug-free layer has been used to enable more uniform release of drug from the implant.

Prototype mold for production of subcutaneous implants

Site-specific, controlled release of therapeutic agents represents an attractive option for companies looking to enhance the efficacy of an existing drug product or provide additional benefit in conjunction with an implantable device. A small but well-established pallet of durable and biodegradable polymeric materials provides options for delivery of potent compounds such as hormones, opioids, antibiotics, and oncology drugs. Well-established silicone rubber and plastic forming processes can be leveraged to make commercial volumes of devices with excellent consistency and reproducibility.

This article was written by James Arps, Ph.D., Director, ProMed Pharma LLC


Jim Arps is a Technical Director at ProMed Pharma, a company engaged in the molding of polymer-based drug releasing implants and combination device components. Working with both established and early-stage medical device and pharmaceutical companies, ProMed develops robust manufacturing processes and platforms for controlled release of therapeutic agents from a variety of materials. For questions please contact him by phone at 763-331-3817 or email at jim.arps@promedmolding.com.