A microcalorimetric investigation of the interaction of surfactants with crystalline and partially crystalline salbutamol sulphate in a model inhalation aerosol system.

Zeyad R Schwen, Julie M Riley, Yaniv Shilo, Timothy D Averch

Index: Pharm. Res. 12(11) , 1689-93, (1995)

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Abstract

The purpose of the work is to study the adsorption of Oleic acid and Span 85 (materials frequently used in aerosols as surfactants) onto partially amorphous and essentially crystalline salbutamol sulphate, attempting to understand the behaviour of metered dose inhalers (MDIs) and observing whether there were any differences in adsorption behaviour and if this could be related to the surface properties of the powder.Isothermal titration microcalorimetry was the principal technique used to measure the adsorption behaviour of surfactants to salbutamol sulphate. A Malvern particle size analyzer was also employed to provide size data on the interactions between the surfactant and powder suspensions.The calorimetric data revealed that surfactant adsorption to the crystalline micronised powder (78% RH and aged dry sample) produced significant exotherms, whereas adsorption to the partially amorphous micronised powder resulted in small heat responses. The differences in adsorption behaviour to the partially crystalline and crystalline surfaces resulted in changes in aggregation behaviour.The stability of MDIs varies depending on the water content, crystallinity and surface composition of the powder. The advantages of using isothermal titration microcalorimetry to evaluate this surface behaviour in such difficult systems was demonstrated.