Measurements of adhesion forces in pharmaceutical powder-polymer systems by atomic force microscopy

Abstract

Atomic force microscopy (AFM) has been adapted to make direct measurements of the pull-off (adhesion) forces between pharmaceutical particles with irregular geometry and rough polymeric surfaces. The measured pull-off force values are used to assist in the selection of materials for production development. The AFM method is advantageous in the duality of information that can be provided. AFM can provide direct measurement of the pull-off force required to remove a single powder particle from a polymer surface. The AFM is also capable of mapping the surface topography with a resolution on the nanometer scale. The study undertaken in this program demonstrates the difficulty and obstacles to be overcome when adapting the AFM technique to irregular particles and substrates with a rough surface. It is established in this work that surface roughness of both powder particles and polymeric substrates has strong effects on the distribution of adhesion force values. A new technique is proposed to identify and analyze the nano-irregularities of particles responsible for contact of particles with flat substrates. The technique is based on nanoindentation of the particle in a thin polymeric film, which is soft and deformable, and the AFM examination of topography of nanoindented mark. Finally, it is shown that capillary condensation of water vapor has a profound effect on particle-substrate interactions at elevated humidity levels.