Investigation of the molecular interactions in a pMDI formulation by atomic force microscopy.

The forces of interaction between inhalable formoterol fumarate dihydrate particles, and the various components of a pressurised Metered Dose Inhaler (pMDI) (e.g. aluminium container, other drug particles and stabilising excipients) were investigated in isolation and combination in the model propellant 2H, 3H perfluoropentane (HPFP). The results obtained offer conclusive proof that the model systems tested have a degree of instability both in the presence and absence of polymer(s). The attractive forces measured following the addition of a mixed homopolymer solution may well be weak enough to be overcome by shaking. The use of homopolymers has inherent difficulties associated with it in the form of bridging interaction. Block or comb copolymers may well be a better option therefore, as they will reduce the possibility of bridging interactions. AFM offers great insight into the behaviour of HFA drug suspensions, and could play a vital role in the future development of suspension formulations.