Particle characterization—the determination of a material’s physical and chemical properties—is a cornerstone of industries such as pharmaceuticals, materials science, biology, and environmental science. Among these properties, particle size is particularly crucial, influencing a material’s performance, stability, and application.
Advances in instrumentation have made particle size analysis more accessible, with efficient and cost-effective tools now widely available. However, achieving accurate measurements requires more than just using advanced technology.
Success hinges on:
● Carefully defining the particle size challenge
● Selecting appropriate instrumentation
● Ensuring proper sample preparation
In this blog, we’ll focus specifically on evaluating a material and achieving a good dispersion to ensure the most accurate particle size measurements.
Particle Terminology
In many industries, the primary particle size—the smallest, indivisible unit of a material that defines its fundamental properties—is often a critical factor. For example, in the pharmaceutical industry, determining the primary particle size is essential for optimizing the bioavailability and manufacturing processes of drug products and raw materials.¹ The physical properties of a final product, such as dissolution rate, uniformity, and stability, can depend heavily on particle size. Similarly, in the paint and ink industries, agglomeration, or the clustering of primary particles, can significantly impact the color strength, appearance, and performance of the final product, such as dried paint or ink.³ Gaining insight into the morphology of the material and the industry-standard definitions is crucial for interpreting particle size data and tailoring materials to specific applications.
Understanding particle size begins with defining the types of particles commonly encountered in materials and observing the material under a microscope. Primary particles can come in various shapes and sizes. For example, a single emulsion droplet or a small, individual particle may be considered a primary particle. However, two fused crystals can also be considered a primary particle (additionally classified as a “hard agglomerate”), as they are bound together so strongly that they cannot be separated and restored to their original form. Figure 1 shows different types of primary particles seen during microscopic observations.
Figure 1. (From left to right) Oil droplets suspended in an aqueous medium, irregular primary, and both irregular crystalline particles dispersed with fused crystal formations that exhibit twinning.
In contrast to primary particles, agglomeration, or groupings of primary particles, can also be a common occurrence within a material. They are typically classified into hard, semi-robust, and soft agglomerates based on how tightly the particles are bound to each other. As noted previously, hard agglomerates consist of fused primary particles. They can negatively impact material properties such as dissolution rate, flow behavior, and overall cohesiveness. Semi-robust agglomerates are clusters that break apart under moderate dispersion forces, such as bath sonication, but these forces may also damage fragile particulate within the sample. Soft agglomerates are the most loosely bound and can often be dispersed with minimal intervention, such as a gentle inversion or the addition of a surfactant to reduce surface tension. Images depicting each type can be found in Figure 2. Generally, the smaller the particle, the more prone to agglomeration the material might be due to increased surface area and increased surface charge.²
Figure 2. (Clockwise from upper left) Well-dispersed primary particles, a soft agglomerate that begins to disperse under a coverslip, hard agglomerate of fused crystals (circled in red), and semi-robust agglomerates composed of crystalline primary particles that are sensitive to excessive force such as sonication.
The Importance of Dispersion
Accurate particle size analysis begins with understanding and addressing the type of agglomerates present in a material. Many instruments, including dynamic light scattering (DLS), laser diffraction, and single-particle optical sensing (SPOS), are dependent on liquid-based dispersions to provide reliable measurements. However, these technologies cannot differentiate between primary particles and agglomerates, making proper dispersion a critical step.
Figure 3. From left to right, examples of a material with semi-robust agglomerates that disperse when a surfactant and bath sonication are applied.
A well-prepared dispersion of particles within a medium ensures that the particles are stable, they do not dissolve or chemically react with the medium, and they remain uniformly distributed throughout the analysis.² Without this, intact agglomerates or flocs can lead to inaccurate data that misrepresents the true properties of the material.
Achieving good dispersion requires breaking apart soft agglomerates into their primary particles while preserving the integrity of fragile particles. This process often begins with gentle techniques, such as inverting or hand mixing the sample, to prevent settling and encourage uniform distribution. For more challenging materials, surfactants can reduce surface tension and aid separation, provided they are carefully selected to suit the sample and carrier fluid.
For samples requiring more aggressive dispersion, advanced techniques such as vortexing and ultrasonication can be used to balance effectiveness with sample integrity. Vortexing delivers consistent agitation through controlled settings, efficiently breaking apart agglomerates.⁴ Ultrasonication, whether performed in a water bath or with a probe, generates ultrasonic cavitation, creating microscopic bubbles that exert mechanical stress to separate particles. While highly effective, ultrasonication must be carefully managed to prevent excessive milling or unintended particle alterations, particularly in high-intensity applications like probe sonication.⁵
In addition to applied force, surfactants and wetting agents are often used in preparations to prevent particles from actively aggregating and to ensure more stable and uniform dispersions. Many work by changing the surface charge of the particulate causing the suspended particles to repel from one another, which allows for a more reliable and accurate particle size measurement.² Figure 3 details a dispersion before the addition of a surfactant and applied sonication.
Conclusion
Achieving proper dispersion is essential for accurate particle size analysis across various industries, from pharmaceuticals to materials science. Without it, agglomerates can lead to misleading data that misrepresents a material’s true characteristics. At PTL, we understand that each sample presents unique challenges, requiring tailored dispersion strategies for reliable, reproducible measurements.
Our method development services customize approaches that maintain sample integrity while effectively separating particles for precise analysis. By mastering dispersion complexities and applying the right techniques, we help clients achieve high-quality data that enhances decision-making and optimizes product performance. Contact us today to get started!
By Kayla Duerr, Particle Characterization Chemist III.
1 Richard N. Kelly and Susan A. Lerke. “Particle Size Measurement Technique Selection Within Method Development in the Pharmaceutical Industry.” Johnson & Johnson Research & Development.
2 ISO 14887: 2000(E) “Sample preparation — Dispersing procedures for powders in liquids”
3 Gary Nichols; “A Review of the Terms Agglomerate and Aggregate with a Recommendation for Nomenclature Used in Powder and Particle Characterization.”
4 “Ultrasonic Devices to Disperse Nanomaterials”
5 Cavitation Erosion of Ultrasonic Probes. http://www.sonics.com, Sonics & Materials, Inc.
