Quantification of Surface Composition and Distribution of Inhalation Powders using TOF-SIMS


Mark Nicholas, Mats Josefson, Magnus Fransson, Jonas Wilbs, Carl Roos, Catherine Boissier and Kyrre Thalberg

Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden


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.

A multivariate TOF-SIMS (time-of-flight secondary-ion mass spectrometry) methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends.

The mass spectrum at each pixel was fitted 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 blended systems have been examined:

  1. coating agents (magnesium stearate, leucine, and sodium stearyl fumarate [PRUV®]) individually blended with carrier lactose
  2. inhalation drugs (beclomethasone dipropionate, budesonide, and salbutamol sulfate) individually blended with carrier lactose

For both kinds of systems, detailed insight into the surface composition and structure could be derived. For the coating agent/lactose systems, TOF-SIMS results were compared with results from a complementary surface analysis technique, XPS (x-ray photoelectron spectroscopy).


  1. Quantification of surface coverage of inhalation powders demonstrated.
  2. Quantification of surface chemical structure of inhalation powders demonstrated.
  3. PRUV® coats lactose carrier as completely but more thinly than magnesium stearate.
  4. 2% salbutamol sulfate coats lactose carrier completely using high shear mixing.