Drug Delivery Device Design and Compatibility with Nitrogen Dioxide Gas Sterilization.

Polymeric materials have become important components in prefilled syringes, drug delivery systems, and advanced medical devices. Background/Objectives: Nitrogen dioxide gas is used for the terminal sterilization of drug delivery systems. For the implementation of sterilization methods, compatibility with materials must be demonstrated such that the materials maintain product requirements and specifications after sterilization and at the time of use (i.e., product shelf life). Methods: Commonly used polymers were selected based on their chemical structures to provide insight into the nature of reactions that occur at the temperature and NO2 concentration levels used in the sterilization process. After exposure to the NO2 process, materials were evaluated for chemical, mechanical, and biocompatibility properties. Results: In this paper, we demonstrated the compatibility of polymers comprising carbonyl, unsaturated ester, and ketone groups which have been used in medical devices sterilized with NO2. No significant chemical or physical changes were observed upon the treatment of Amorphous Polyester, Polysulfone (PSU), Polycarbonate (PC), PolyEtherEtherKetone (PEEK), PolyArylEtherKetone (PAEK), and Polypropylene (PP) with NO2 at a sterilization temperature of 20 °C. At this relatively low sterilization temperature, the reactions of NO2 with the polymer do not typically occur because the activation energies of these reactions require much higher temperatures. Conclusions: Not all materials will be compatible with NO2 sterilization, and even with the established data, many devices will need to have their polymers evaluated for compatibility before moving to NO2 sterilization. These results will provide guidance to device designers selecting materials for new drug delivery devices and to regulators that review the safety and efficacy of these devices.