FRACTAL MORPHOLOGY OF DRUG AGGREGATES IN AEROSOL PROPELLANT SUSPENSIONS

The study and formulation of drug suspensions in aerosol propellants is frequently hampered by lack of information concerning the structure and properties of the aggregated drug particles in suspension. We describe apparatus for the photomicrographic study of aggregates in suspension of volatile liquids, and apply this technique to measure the fractal properties of the drug aggregates. The boundary fractal dimensions of such flocs indicate that the model drugs studied (lactose and salbutamol sulphate) aggregate by a diffusion limited cluster-cluster mechanism in the absence of surfactants. However in the presence of Span 80, a typical surfactant used in aerosol systems, the morphology of the aggregates is significantly altered. The tenuous convoluted flocs become more compact and spherical. This is characterized by a reduction in the boundary fractal dimension, suggesting that considerable flee rearrangement occurs during aggregation. This implies that the surfactant reduces bonding forces between drug particles, allowing dynamic changes in flee structure.