Particle Size Characterization of Individual Components in Co-Micronization Blends of APIs with SPES Technology
How single particle optical analysis resolves the size distribution of each API and excipient inside a co-micronized blend.
Many APIs need both particle size control and an excipient to reach adequate solubility and bioavailability. Blending micronized powders is not simple: cohesive forces make fine particles hard to mix. Co-micronization solves this by feeding API and excipient together into a spiral jet mill, where they are reduced in size and blended in the same step.
This creates a new analytical question. Once the components are milled together, standard particle size methods measure the blend as a whole. They do not show how each component contributes to it.
This white paper, co-published by Micromacinazione and Microsize in collaboration with EOS Instruments, addresses that question. Five blends were co-micronized on a 4" spiral jet mill at 90 PSI: diphenhydramine HCl with SYLOID® (50:50, 95:5 and 99:1), with hypromellose (25:75) and with acetaminophen (50:50). Each component was also milled separately under the same conditions.
The blends were analyzed with the Classizer™ ONE, based on SPES (Single Particle Extinction and Scattering)technology. SPES measures the light scattered in the forward direction by one particle at a time and extracts two optical parameters for each particle: the extinction cross section and the polarizability. Plotted together, they form a two-dimensional map, the EOS Cloud, where particles that differ in size or refractive index fall in different regions.
In the diphenhydramine HCl/SYLOID® blends, the difference in refractive index between the two materials made it possible to separate the two populations and obtain the particle size distribution of each component, in all three ratios. For blends where the refractive indices are close, as with hypromellose and acetaminophen, a Principal Component Analysis (PCA) approach still identified the contribution of each component. The PCA also distinguished all three API/excipient ratios, including 99:1.
For more background on the measurement principle, see Potenza et al., 2015 and Villa et al., 2016.
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