Kjellberg, Karolina Charlotte; (2010) Microparticle Adhesion in Model Metered Dose Inhalers. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The factors that influence particle adhesion in model metered dose inhalers (MDI) have been investigated and models that predict the adhesion have been evaluated. Particle adhesion to the canister wall was correlated with Gibbs free energy of interaction based on surface energy parameters from sessile drop contact angle analysis, interaction parameters based on Hansen solubility parameters from Stefanis' group contribution method, forces of interaction from atomic force microscopy measurements and the physicochemical properties of the MDI components. Non-pressurised model propellants were used throughout the study and simplified model formulations were studied consisting of two components, a powder compound (beclomethasone dipropionate, budesonide, terbutaline sulphate, polyacrylic acid and polyvinylalcohol) and a model propellant (2H,3H-perfluoropentane, perfluoroheptane and perfluorodecalin) that were filled into different canisters (polyethyleneterephtalate, aluminium, anodised aluminium, perfluoroalkane coated aluminium and glass). The true adhesion of microparticles in model MDIs was studied with a method developed here and significant differences (p<0.05) in adhesion were found between the different MDI systems studied (0.02 - 47.6%w/w). It was also found that the adhesion reached a maximum within 60 minutes. Among the methods for predicting interactions Gibbs free energy of interaction calculated using the surface component approach resulted in the best predictions of adhesion trends. It was found that even low polarity of materials involved had an important impact on the predicted interactions. Both apolar and polar energies of interactions were important to consider and the energy of interaction of particle-canister immersed in a liquid (ΔG132) and the energy of interaction of particle-particle immersed in a liquid gave the best predictive model for the true adhesion in model MDIs since the interactions considered the intermaterial interactions in presence of the liquid. The linearity found when plotting the true adhesion of particles to a canister material against ΔG132 was considered good (R2 0.6855 - 0.9987).

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