A MICROCALORIMETRIC STUDY OF SURFACTANT AGGREGATION AND SURFACTANT DRUG-INTERACTION IN A MODEL INHALATION AEROSOL SYSTEM

Two surfactants, oleic acid and Span 85, have been diluted from concen trated solution in Arcton 113 by gradual titration into Arcton 113 in a titration cell of an isothermal microcalorimeter. The heat of diluti on responses revealed areas of interest in which it can be assumed tha t the state of aggregation of the surfactants changes. These points ar e at concentrations of approx. 0.3 and 0.7% w/v for oleic acid and at 0.8% w/v for Span 85. The experiments were repeated with salbutamol ba se suspended in Arcton 113, such that the adsorption of surfactant to the drug could be investigated. For both surfactants the results when drug was present were significantly different from those when drug was absent (dilution only). for oleic acid the data with drug were more e xothermic and for Span 85 they were more endothermic, indicating diffe rent thermodynamics of adsorption for the two surfactants. For both su rfactants there were break points in the adsorption data at concentrat ions corresponding to the break points in the dilution data. It can be concluded that the adsorption process is highly dependent upon the st ructure of surfactant in solution. For both surfactants the critical c oncentration was at or just below the value of 1% that has been found to be an effective surfactant loading for the production of inhalation aerosols. This data provides an explanation for the practical observa tion on surfactant use and demonstrates that microcalorimetry is a val uable technique for studies on these difficult systems.