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

加压定量吸入器（pMDI）是用于治疗各种肺部疾病和病症（例如哮喘和COPD）的药物递送装置。一个典型的装置包括一个罐，计量阀，和一个执行器。在罐内是加压推进剂和药物，其存在于溶液（溶解在推进剂中）或悬浮液（分散在推进剂中的固体颗粒）中。pMDI通过计量阀的压下产生可吸入气雾剂，导致在计量室（含有药物成分和推进剂的混合物）和大气之间形成开口。腔室和大气之间的压力差导致混合物快速喷射和蒸发，从而形成雾化羽流，然后由患者吸入以将治疗输送到肺部。有几个因素会影响这一过程，并导致剂量一致性和罐内制剂稳定性的变化。这些因素包括湿度、推进剂的变化（CFC到HFA）以及药物/推进剂与吸入器组件的长期接触，例如，研究的一个领域涉及包含药物成分的铝罐的内表面的处理，降低铝催化的药物降解或由于粘附到罐表面的药物损失的风险。存在许多表面涂层技术;然而，本项目将集中在最近的，采用等离子体涂层存款碳氟聚合物（FCP）的罐的内表面。与其他涂层技术相比，这具有较低的环境影响，并且可以提供更好的吸入器性能。然而，没有关于以下方面的公开研究：i）等离子体处理的罐表面的特性和均匀性，尤其是具有不同等离子体涂层参数的情况; ii）处理如何影响药物颗粒对罐表面的粘附; iii）等离子体处理对药物递送和稳定性的影响。对这些问题的更好理解将使等离子体过程能够针对不同的药物和配方进行优化。本项目将使用一系列实验技术来研究这三个不确定性领域。将采用一系列显微技术（包括：SEM、AFM、3D）和表面化学研究（包括XPS和接触角测量）。AFM还将用于量化各种药物对不同罐表面的粘附。所有这些研究的结果将与药物递送和稳定性研究的结果进行三角测量，以确定血浆涂层参数、表面特征和吸入器性能之间的关系。

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.