A key concern for the use of bioresorbable materials is the presence of water or moisture within an bioresorbable device. As the majority of bioresorbable polymers degrade by hydrolytic degradation, minimizing water content is of the utmost importance for enhancing device life and maintaining functionality. In general, bioresorbable polymers degrade by bulk hydrolysis of main-chain esters. This hydrolysis occurs throughout the length of the polymeric chain, gradually reducing the chain length. Excessive moisture in absorbable products leads to change in device functionality through a reduction in polymer molecular weight, loss of strength, mass loss, and a shortened lifetime of the device. To extend the life of bioresorbable medical devices, drying is a critical parameter to enhance the shelf-life and stability of a product. In general terms, drying means the removal of relatively small amounts of water or other liquid from a solid material to reduce the content of residual liquid to an acceptably low value. Drying is usually the final step in manufacturing and the product is often ready for final packaging following drying. Drying parameters that influence the process include temperature, humidity, diffusion coefficient of material, and device features such as surface area, microporosity, and bulk mass within the vacuum oven (lot size of your device) to name a few. Drying methods include three main procedures: 1) placement of products in vacuum under reduced pressure (atmosphere), 2) use of desiccant, 3) use of heat to drive evaporation of water as well as and any combination therein. The desired drying method ultimately depends on the device configuration and the desired moisture level. Application of heat can be used to drive off moisture but can also have undesired effects on delicate and sensitive products.
1) Vacuum Drying: placing your medical device in a reduced atmosphere environment is a well-known means to remove moisture from products. Adequate vacuum drying requires low vacuum levels to be reached and maintained (<1.5 Torr) throughout the drying cycle. This process can require extensive time periods to remove inherent moisture depending on the device configuration. Nitrogen purging is used to replace ambient air with pure N2 (dry air) removing ambient moisture and lowering the surrounding humidity of the environment; this method is almost always combined with vacuum drying as removal of ambient air and back-filling with dry air does not re-saturate your device and provides a moisture free environment;
2) Desiccants are hygroscopic materials that induce or sustain a state of dryness in its vicinity and are used due to their non-toxic and odorless nature; common desiccants include silica gels, Zeolite, and montmorillonite clay each adsorbing upwards of 40% of their weight in water vapor at 100% humidity. Desiccants can also be placed within a device’s final packaging configuration (packaged within a Tyvek® substrate) to maintain a dry environment;
3) Application of heat is another means to drive off excess moisture through evaporation and can take place at elevated temperature usually near or at the boiling point of water and can range from 60-100°C; though heating will drive off moisture it should not be used for devices constructed from polymers with low melting points or fine features, where heat could distort the functionality of the device; heating can also be combined with vacuum drying to accelerate the removal of moisture;
To validate a drying cycle, moisture content in your device is quantified using the method known as Karl Fischer (KF) titration. KF is a classic titration method in analytical chemistry that uses coulometric or volumetric titration to determine trace amounts of water within a sample. KF is commonly used based on its high accuracy and precision, selectivity for water, small sample size required (>1g), and large detection range (0.01% (100 ppm) to 100%). A key parameter to be aware of with this method is the ambient temperature and humidity at which the measurement and test method takes place, as this can cause samples to rapidly adsorb moisture from the surrounding environment. As a precaution and to limit the effect of rapidly adsorbed moisture, nitrogen purge steps can also be implemented with this procedure.
The final choice of drying parameters (length of time/ method) is determined on a case by case basis taking careful consideration of all aspects of device design including material (polymer) selection, device indication, device features, and desired shelf life. Regardless of the method chosen, each drying cycle must be validated to assure consistently reliable moisture specifications can be achieved for the particular device and packaging configuration prior to market launch. When dealing with absorbable materials, the choice of drying method can be difficult and complex as it is coupled with the sterilization method of your device, packaging configuration, and desired shelf life.
An incorrect choice in drying parameters can potentially lead to a limited product shelf life and a limited return on investment on development expenditures. Poly-Med (www.Poly-Med.com) offers a breadth of bioresorbable polymer knowledge to fully support our clients throughout the complete lifecycle of a new medical device. To leverage our experience to help with your drying questions, feel free to contact us today.