Quantification of surface composition and surface structure of inhalation powders using TOF-SIMS

A multivariate TOF-SIMS methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends. Surface properties are often critical to the behavior of powder formulations, especially in the case of dry powders for inhalation, as surface properties directly affect inter-particulate forces and, hence, the dispersibility of the formulation. The mass spectrum at each pixel was fit to a linear combination of reference spectra obtained by non-negatively constrained alternating least squares. From the pixel compositions, average surface coverage and a range of other image features were calculated. Two kinds of systems have been examined: 1) binary blends of lactose particles and coating agents, and 2) blends of different inhalation drugs with carrier lactose. For both kinds of systems, detailed insight into the surface composition and structure could be derived. For the former study, TOF-SIMS results were compared with a complementary surface analysis technique, XPS.