Methods for manufacturing implants that minimise the risk of infection
Andrew Gaillard, Trelleborg Sealing Solutions, examines the tests which prove that the immersion method is effective for the manufacture of implantable devices.
Healthcare-associated infections (HAI) are a major, yet often preventable threat to patient safety and they can have a significant impact on the survival rate of patients who undergo procedures and treatments. In particular, catheter-associated infections are difficult to prevent, even when products are made of silicone, due to their inherent positioning both inside and outside of the body.
Though silicone is biocompatible and bio-stabile, it is not immune to bacterial colonisation. Three techniques exist that can reduce this colonisation. These are coating with active pharmaceutical ingredients (APIs), the addition of API to raw silicone, and the impregnation of vulcanised silicone with API through immersion.
Coatings of API are applied to silicone catheters by spraying or dipping. Though probably the most cost-effective method of treatment, achieving good uniformity and long life is challenging. Cracking or peeling of coatings may occur and in some cases, it can be hard to apply a coating to the inner lumen surface of a catheter.
The second and well-proven method used to prevent bacterial buildup involves the adding of antibiotic API, such as chlorhexidine, gentamycin, xifaxin, and doxycycline in powder form to silicone raw materials using various types of mixing equipment. After homogenisation, the silicone drug mixtures can be formed into desired shapes and vulcanised using various fabrication processes including moulding and extrusion.
The key advantage of this method is that the API is effectively and consistently present within the silicone. However, compatibility of the API with the silicone grade needs to be confirmed as some API can inhibit or even poison the cure system of certain silicones. Also, particular drugs are not stable at elevated temperatures. In these applications, silicones that can be vulcanised at relatively low temperatures may be utilised, but this limits the type of API that can be used.
The third and newest method to reduce bacteria colonisation is the impregnation method. The vast majority of silicone medical components are manufactured from raw material formulations containing polydimethylsiloxane (PDMS) polymers reinforced with amorphous noncrystalline silica. Vulcanised PDMS elastomers can be readily swollen by immersion in various organic solvents. Using this characteristic, vulcanised silicone can be immersed in a solution containing API to impregnate the vulcanised silicone with active drugs.
The advantage of the impregnation method of vulcanised silicone with API is that the API cannot interfere with the cure chemistry of the silicone and that the API is uniformly impregnated on the surface of the inner lumen.
Immersion is usually conducted at room temperature, thereby eliminating concerns regarding the thermal degradation of the API, expanding the types of APIs that can be used. In addition, dissolved drugs are impregnated within the silicone elastomer as discrete molecules. Concerns and costs associated with specifying and maintaining a particular size and distribution of particles are minimised.
Immersion experiments have conclusively demonstrated the mass transfer of two antibiotics: Clindamycin Hydrochloride (CLIN) and Rifampicin (RIF) from chloroform solutions to silicone tubing. Following on from these tests, a study of the Kirby-Bauer Zone of Inhibition (ZOI) assessed the impact of drug content of silicone tubes on the gram-positive coccal bacterium, Staphylococcus aureus.
The results of this study showed that drug-impregnated tubing had a powerful inhibitory effect on the growth of Staphylococcus aureus and clear zones of inhibition were seen surrounding test articles. As expected, the higher the drug concentration, the larger the Zone of Inhibition (ZOI). Though still in the early stages of usage, the impregnation method looks positive, potentially allowing the expansion of the drug types that can be delivered via silicone implantable devices.