A fundamental study of the interactions between binary particulate formulations in HFA-based pressurised metered dose inhaler (pMDI) systems was undertaken. Differences in the surface energetics of lactose, mannitol and sibenadet hydrochloride were observed, which could be related to the degree of particle adhesion/cohesion, the sedimentation rate and the aerosolisation performance of formulations containing different mixtures of these components. In general, lactose was shown to be the most cohesive material and readily formed coarse aggregates with sibenadet hydrochloride which sedimented rapidly. This had the greatest effect on aerosolisation performance at high-lactose concentrations (and low-sibenadet hydrochloride concentrations), where heavily agglomerated particles were observed in collected samples of the emitted aerosol. A model, relating the adhesive and cohesive forces between the components in these systems has been proposed, which satisfactorily describes these phenomena. Furthermore, although the more energetic systems were shown to result in significantly decreased aerosol performance, the through-life performance was enhanced. (C) 2009 Elsevier Ltd. All rights reserved.