Atomic Force Microscopy

An analytical technique that is receiving increased attention in the pharmaceutical industry is atomic force microscopy. We interview Mark Leaper from the UK's De Montfort University to find out more about this technology.
May 01, 2012

What is atomic force microscopy? What are its advantages and disadvantages?

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Atomic force microscopy (AFM) relies on passing a sharp probe, mounted on a cantilever, over a surface to analyse its topography. A laser is reflected off the back of the cantilever, and the variations are measured by a photodetector and interpreted by software. The characteristics of the probe and cantilever can be varied according to the test sample. The mode of operation can also be changed, so that the probe can contact the surface continuously (contact mode), tap the surface intermittently (tapping mode), or hover above the surface (contact mode). The technique can also be used to analyse the adhesion, cohesion, stickiness and hardness of surfaces. The main advantage of using this method is that no prior preparation of the sample is required, so the dynamics of any changes can be monitored. Under the right conditions, the z-axis resolution can be close to atomic level. The main disadvantage is that the area of measurement cannot exceed 100µm by 100µm.

Mark Leaper
A comprehensive review of the applications of AFM can be found in the book "Atomic Force Microscopy in Process Engineering", edited by Professors Richard Bowen and Nidal Hilal. This also contains a chapter on the latest studies of AFM in a pharmaceutical context.

How is AFM being used for the qualitative and quantitative analysis of pharmaceutical powders?

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.

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