Polymorph Characterization by Particle Size Analysis (PSA)
Although optical microscopy and SEM analysis can reveal particle sizes, they can image only a small number of grains, which greatly limits their accuracy, especially for size distribution analysis. PSA, by comparison, examines many millions of grains, thus providing an enhanced statistical analysis, even for samples with multimodal particle size distribution. Modern instruments perform PSA using laser diffraction methods that can analyze the range of 0.01 to 3,000 micrometers at high speed.
Our laboratory uses a modern Horiba LA950 V2 particle size analyzer that relies on laser diffraction. Under normal operation, the test powder is suspended in a carrier liquid containing a surfactant and ultrasonicated to break up agglomerates. But if the test powders dissolve in the carrier liquid, they are run dry, where the de-agglomeration is carried out by an ultrasonic vibrator and a high pressure air shear. Thus, even very moisture sensitive materials can be tested down to 10 nm average particle size. Typically, scans are run in triplicate to insure that complete de-agglomeration has occurred and that the data are stable.
Multimodal Particle Size Distribution Analysis
One of the more challenging problems is the measurement of test samples that exhibit a multimodal particle size distribution such as that shown to the left. As clearly seen, there are fines with a median size of 0.18 microns, intermediates with a median of 94 microns and large particles with a median of 385 microns.The plot also shows the spread of each particle size mode in the sample. Further analysis of these data also reveal the cumulative weight fraction of particles below a given mean diameter (shown as the solid line in the Figure).