The Effect of Surfactant and Solid Phase Concentration on Drug Aggregates in Model Aerosol Propellent Suspensions

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Abstract
The effect of increasing solid phase concentration on the morphology and flocculation rate of model aerosol suspensions has been investigated. Suspensions of micronized salbutamol sulphate and lactose in trichlorotrifluoroethane (P113) were studied under conditions of increasing shear stress. By use of image analysis techniques, measurement of aggregate size, fractal dimension and rate of aggregation was performed. The effect of the surfactant sorbitan monooleate on morphology and flocculation rate was also studied. Increased solid phase concentration caused an increase in the rate of aggregation and average aggregate size at a given value of shear stress. Surfactant addition retarded the aggregation rate, and caused a shift from a diffusion-limited cluster aggregation to a reaction-limited cluster aggregation mechanism. The aggregate profiles showed a corresponding change from rugged and crenellated without surfactant, to increasingly smooth and Euclidian with increasing surfactant concentration. The morphological changes were characterized by a decrease in the average boundary fractal dimension which also correlated well with the corresponding reduction in aggregation rate.