A study on drug deposition mechanisms of pre-treated pMDI canisters

High performance of inhalation devices is essential to inhalation therapy. Pressurised Metered Dose Inhalers (pMDIs) are the most commonly used devices due to low cost, portability, and easy use. However, one of the main drawbacks of these devices is drug deposition phenomena appearing on pMDI hardware. Thus, the aim of this project is to explore drug deposition mechanisms on aluminium canisters employed with Pressurised Metered Dose Inhalers (pMDIs). The investigation explored the influence of various surface treatments, applied to the canisters, to drug deposition phenomena. The Active Pharmaceutical Ingredient (API) examined was salbutamol sulphate, suspended in a model 2H, 3H, decafluoropentane propellant. Physicochemical characterisation of the canisters was performed after the application of different surface treatments, to explore potential links between: surface topography, surface chemical composition, total surface energy, and drug caking appearing on the canister walls. The coating treatments which were tested were; Fluorinated Ethylene Propylene (FEP) lacquer, vapour deposited Parylene C, PES coating, 3M-proprietary, fluid-applied fluorosilanes, and fluorocarbon coating deposited through plasma enhanced chemical vapour deposition. Anodisation and silane pre-treatment were also explored, both with and without additional fluorosilane treatment. A number of surface physicochemical characterisation techniques were employed, namely; Scanning Electron Microscopy (SEM), Focused Ion Beam (FIB), Atomic Force Microscopy (AFM), X-Ray Photoelectron Spectroscopy (XPS) and Contact Angle (CA) analysis. The data from these analyses were correlated with those from a Drug Deposition test employing drug quantification by UV spectrophotometry. Topographical profile of drug deposition on treated canisters was also studied with the use of SEM technique. The research concluded with direct correlation of drug deposition phenomena with surface topography, surface chemistry, and surface free energy. High surface roughness resulted in mechanical interlocking of drug particles and drug particle entrapment inside topographical surface features. Upon high Relative Humidity (RH) increase of drug adhesion and cohesion phenomena were observed, due to water ingress inside surface topography. Also, high percentages of fluorine on surface chemistry, are really promising for non-stick performance of treated canister. Finally, direct correlation of surface free energy with drug deposition was observed. Upon high surface free energy, increase of drug deposition was observed, while for low surface free energy, insignificant drug caking phenomena occurred to surfaces of contact. The lowest total surface free energy values and lowest deposition values were seen when the 3M fluorosilane coating was applied as a final treatment combined with silane pre-treatment, either on PES substrate, or on alumina substrate. Enhanced performance of FEP coating was also observed. This research resulted to propose a new combination of surface treatments for canisters of pMDI hardware. In specific, PES substrate combined with silane pre-treatment, and 3M fluorosilane surface treatment was proposed for canisters of the hardware of the device, also patented by the 3M Company.