Using AFM in Pharmaceutical Studies of Drug Crystal Growth, Particles, and Coatings (AN63)

Microscopic evaluation is important for the design and evaluation of a pharmaceutical product after the steps in the drug formulation process. Since atomic force microscopy (AFM) provides the ability to directly investigate surface structure at nanometer-to-subangstrom resolution in ambient and liquid environments, it has been applied to a wide range of pharmaceutical research, and delivers a powerful complement to other common analytical techniques. This application note describes the use of AFM from the studies of drug crystal growth, particle characterization, and tablet coatings in the manufacture of solid dosage forms.

AFM is performed by scanning a sharp tip on the end of a flexible cantilever across a sample surface, while maintaining a small, constant force. Tip types vary depending on application requirements, but they typically have an end radius of 5 to 10 nanometers. In a basic AFM setup, a piezoelectric tube scanner scans the tip in a raster pattern over the sample. Tip-sample interaction is monitored by reflecting a laser off the back of the cantilever onto a split-photodiode detector. Over the past several decades, a variety of scanning modes have been developed to control how the tip scans the sample. Contact mode and TappingMode™ are two of the more commonly used AFM techniques of operation.