What is atomic force microscopy? What are its advantages and disadvantages?
By attaching a powder particle to a blank cantilever to create a "colloid probe", the interactions of the particle with other particles, equipment surfaces, and membranes can be measured. This can help with operations such as tablet compression, interactions of carrier particle with APIs in pulmonary drug delivery and interaction of excipients with membranes.
The micromechanical properties of particles can also be assessed by pressing the probe into the surface of the particle to reveal the hardness and stickiness of the surface. This can be done under controlled temperature and relative humidity. Because the sample requires no preparation, it's possible to obtain the dynamic responses to temperature and relative humidity changes for the same area.
In what ways does the force measurement aid the study of particle interactions between drugs and excipient particles?
As explained above, the technique can be used to examine the surface adhesion, cohesion, stickiness, and hardness of particles at varying humidities and temperatures. This can be done both in liquid and in air. It's also useful for assessing the interactions between the particles in solid dosage forms. The main applications, however, are in designing systems in which APIs are attached to inert carrier particles for pulmonary drug delivery. It's also useful for examining the effectiveness of dry granulation systems, to which interparticle forces are important.
How does AFM compare with other particle characterisation techniques, such as laser diffraction or Raman spectroscopy?
AFM should be used as complementary to such techniques, rather than as an alternative. AFM is primarily focusing on the surface properties of particles and topography, whereas the other techniques are used to identify the chemical composition of the entire particle, or the structure of the crystals/molecules present. AFM gives no indication of the degree of crystallisation or water content, but may indicate areas of different physical properties, which can be investigated further, using other methods. This can be useful in systems that are changing from an amorphous to a crystalline nature. AFM can detect the zones on the particle where this is taking place and other techniques can be used to examine this further.