Investigation of The Surface Properties of Plasma Treated Pressurised Metered Dose Inhaler Canisters and Their Influence on Formulation Performance

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Pressurised metered dose inhalers (pMDIs) are drug delivery devices used in the treatment of various lung diseases and conditions such as asthma and COPD. A typical device consists of a canister, a metering valve, and an actuator. Within the canister is the pressurised propellant and drug which exists in either a solution (dissolved in propellant) or suspension (solid particles dispersed in propellant). pMDIs generate an inhalable aerosol through the depression of the metering valve, causing an opening to form between the metering chamber (containing a mixture of pharmaceutical ingredients and the propellant) and the atmosphere. The difference in pressure between the chamber and the atmosphere causes rapid ejection and evaporation of the mixture, thus forming an aerosolised plume that is then inhaled by the patient to deliver treatment to the lungs. Several factors can affect this process and result in changes in dose consistency and the stability of the formulation within the canister. These include humidity, changes in the propellant (CFCs to HFAs), and drug/propellant's prolonged contact with the inhaler components, e.g., the canister aluminium surface and metering valve.One area of investigation relates to treatments of the internal surface of the aluminium canisters that contain the pharmaceutical ingredients, reduce the risk of aluminium-catalysed drug degradation or drug loss due to adhesion to the canister surface. Many surface coating techniques exist; however, this project will focus on the most recent, which employs plasma coating to deposit a fluorocarbon polymer (FCP) on the internal surfaces of canisters. This has a lower environmental impact and may give better inhaler performance compared to other coating techniques. However, there is no published research into i) the characteristics and uniformity of plasma treated cannister surfaces, especially with different plasma coating parameters; ii) how the treatment affects the adhesion of drug particles to the cannister surface; iii) the effects of plasma treatment on drug delivery and stability. A better understanding of these issues would enable the plasma process to be optimised for different drugs and formulations .This project will investigate these three areas of uncertainty using a range of experimental techniques. Surface characteristics and uniformity will be investigated with a range of microscopic techniques (incl. SEM, AFM, 3D) and investigations of surface chemistry (incl. XPS and contact angle measurement). AFM will also be used to quantify the adhesion of a variety of drugs to different canister surfaces. Findings from all these studies will be triangulated with the findings of drug delivery and stability studies, to determine the relationship between plasma coating parameters, surface characteristics and inhaler performance.