THE USE OF SURFACE-ENERGY AND POLARITY DETERMINATIONS TO PREDICT PHYSICAL STABILITY OF NONPOLAR, NONAQUEOUS SUSPENSIONS

Suspensions of five model micronised particles (indomethacin, isoprenaline, aspirin, polytetrafluorethylene (PTFE) and beclomethasone, which were selected for their range of surface energies and polarities) in a non-polar, non-aqueous liquid (Arcton 113 - a model aerosol propellent) were prepared and assessed for ease of solid dispersion, tendency for solid aggregation and the extent of adherence of solid to the container walls (the effect of coating the container walls in order to alter its surface energy and polarity was also investigated). The surface energies and polarities of all the solids, the materials used to make and/or coat the container, and Arcton 113 were estimated from the necessary contact angle and surface tension measurements. The experimentally observed properties of the suspensions were compared to the theoretical interactions, i.e., ease of dispersion was found to correlate with the work of cohesion of the particles and the spreading coefficients of the powders over Arcton 113; the extent of aggregation of the particles correlated with their polarity (and was unrelated to the liquid properties), whilst the extent of adherence of particles to the surface of the container correlated with the difference between the works of adhesion between the particles and the container and the works of adhesion between the particles and Arcton 113 (changing the surface properties of the container resulted in different extents of adherence, but all results approximately fitted one master curve). By obtaining estimates of surface energies and polarities, it should be possible to predict the ease of manufacture and the physical stability of many non-aqueous, non-polar suspensions, such as metered dose inhaler products. It is well known that processing (e.g., milling) can affect powder surface energies, and the possibility that processing stages can be planned to optimise a product's physical stability is discussed.