Comparative study of erythritol and lactose monohydrate as carriers for inhalation: Atomic force microscopy and in vitro correlation

Abstract

The adhesion of micronised salbutamol sulphate to two carrier excipients, lactose monohydrate and erythritol, was investigated using the atomic force microscope (AFM) colloid probe technique and correlated with their respective physico-mechanical properties and aerosolisation performance. The particle size, morphology and moisture sorption properties of the carriers were similar thereby allowing direct comparison of functionality. AFM force measurements ( n = 1024 force curves) were obtained between salbutamol sulphate drug probes ( n = 4) and the excipients, as 63–90 μm sieve fractions and atomically smooth crystals. In general, significant differences in drug adhesion to lactose monohydrate and erythritol were observed (ANOVA, p < 0.05), with erythritol exhibiting relatively greater adhesiveness. A linear relationship between drug probe adhesion to lactose monohydrate and drug probe adhesion to erythritol was established with salbutamol sulphate–lactose monohydrate adhesion being 60–70% of that of the erythritol system. In vitro analysis suggested good correlation with the adhesion measurements. The aerosolisation of salbutamol sulphate from erythritol carrier particles was significantly less (ANOVA, p < 0.05) than from lactose monohydrate, with a fine particle dose (<6.4 μm) of 41.9 ± 7.4 μg and 24.9 ± 3.1 μg for the lactose monohydrate and erythritol carriers, respectively ( n = 3).