Scanning white-light interferometry as a novel technique to quantify the surface roughness of micron-sized particles for inhalation

A novel approach of measuring the surface roughness of spherical and flat micron-sized drug particles using scanning white-light interferometry was applied to investigate the surface morphology of micron-sized active pharmaceutical ingredients (APIs) and excipient particles used for inhalation aerosols. Bovine serum albumin (BSA) and alpha-lactose monohydrate particles were chosen as model API and excipient particles, respectively. Both BSA and lactose particles were prepared with different degrees of surface corrugation using either controlled spray drying (four samples of BSA) or decantation (two samples of lactose). Particle size distributions were characterized by laser diffraction, and particles were imaged by scanning electron microscopy (SEM). Surface roughness of the BSA and lactose particles was quantified by white-light optical profilometry using vertical scanning interferometry (VSI) at full resolution using a 50x objective lens with 2.0 x and 0.5 x fields of view for BSA and lactose, respectively. Data were analyzed using Vision software (version 32, WYKO), and surface roughness values are expressed as root-mean-square roughness (R-rms). Furthermore, data were compared to topographical measurements made using conventional atomic force microscopy. Analysis of the optical profilometry data showed significant variation in BSA roughness ranging from 18.58 +/- 3.80 nm to 110.90 +/- 13.16 nm for the smoothest and roughest BSA particles, respectively, and from 81.20 +/- 15.90 nm to 229.20 +/- 68.20 nm for decanted and normal lactose, respectively. The R-rms values were in good agreement with the AFM-derived values. The particle morphology was similar to SEM and AFM images. In conclusion, scanning white-light interferometry provides a useful complementary tool for rapid evaluation of surface morphology and roughness in particles used for dry powder inhalation formulation.