The development of a novel metered dose inhaler cyclic olefin copolymer elastomer sealing system

Authors: , , , , ,

The objective of this work was to develop a new and improved sealing system for MDI (metered dose inhaler) products. The sealing of a metered dose valve to a canister in an MDI is a key part of the overall integrity of the MDI system and has historically been most frequently done using nitrile (black or white) or EPDM (ethylene propylene diene monomer) seals. The main MDI sealing system ensuring the container closure between the metered dose valve and the canister could influence many attributes of the resulting MDI including moisture content, leak rate, impurities and degradation products, dose content uniformity, particle size distribution (or fine particle mass) and extractable & leachables.
The potential for moisture to contribute to instability and particle aggregation in non-aqueous pharmaceutical aerosols formulations is well known [1], and minimizing moisture ingress and content are of interest in order to develop and manufacture stable aerosol formulations. The cleanliness of the materials used in the MDI container closure system, and minimizing extractables and leachables are also seen by regulatory authorities as key elements with regard to both safety [2] and eventual stability of the MDI products [3]. In addition any sealing system for MDIs has to have low long term leak rates over a wide range of environmental conditions.
This work describes the development of an innovative sealing material, cyclic olefin copolymer elastomer (COCe), which can offer several advantages in terms of the overall performance of the MDI system, specifically with regard to moisture resistance and cleanliness and thus eventually to the overall stability and performance of such MDI products incorporating this kind of valve to canister sealing technology. Key performance characteristics were studied such as leak rates, moisture ingress, extractables and compatibility with different HFA (hydrofluoroalkane)/ethanol ratios as well as other manufacturing related parameters such as crimping and recycling have also been investigated.
Cyclic olefin copolymers [4] are a new class of polymeric materials with property profiles which can be varied over a wide range during polymerization. These new materials exhibit a unique combination of properties which can be customized by varying the chemical structure of the copolymer. Interesting performance benefits for MDI applications could be considered as – low water absorption, excellent water vapour barrier properties, rigidity, strength and compression set, excellent biocompatibility, good resistance to acids and alkalis and their ability to be moulded into specific component parts. COCs have already found successful industrial applications in the parenteral drug arena and their unique combination of properties, detailed above, make them ideal solutions for applications such as prefilled syringes…