Particle Size Analysis: Methods, Standards, and How Labs Report PSD

This article has been revised to reflect the latest industry updates, including the ISO 22412:2025 revision and the proposed USP <429> harmonization.

A drug powder dissolves more slowly than its last batch. A cement lot sets too fast. A metal additive manufacturing powder spreads unevenly across the build plate. Each problem can trace back to the same variable: How big the particles are, and how those sizes spread across the sample.

Particle size analysis measures that variable. Labs report the result as a particle size distribution (PSD), usually summarized as D10, D50, and D90 values. The method behind those numbers matters as much as the numbers themselves. A 2022 peer-reviewed comparison of six metal powders found that laser diffraction and imaging instruments produced spreads wider than industrial tolerances allow, even for mostly spherical particles.

Key Takeaways

• Particle size analysis and PSD testing describe one discipline. The analysis is the measurement; the distribution is the result.
• Ensemble methods such as laser diffraction and dynamic light scattering (DLS) measure many particles at once. Counting methods such as image analysis measure particles one by one.
• ISO 13320:2020 remains the current laser diffraction standard after ISO confirmed it in 2025.
• ISO 22412:2025 replaced the 2017 DLS standard and added multi-angle and imaging DLS.
• USP <429> has a pending harmonized revision that would retitle the chapter and rewrite its instrument qualification section.
• USP <786> analytical sieving suits powders where at least 80% of particles are larger than 75 µm.
• Different methods define “size” differently, so results from two techniques rarely match for non-spherical particles.
• Requesters who name the method, dispersion conditions, and reporting basis receive results they can compare across labs and batches.

What Is Particle Size Analysis?

Particle size analysis determines the sizes of particles in a powder, suspension, emulsion, spray, or aerosol. Particle size distribution (PSD) is the output: The proportion of material in each size class. Many sources treat “particle size analysis” and “PSD testing” as separate tests. In practice, they describe the same work. The analysis is the measurement, and the distribution is what the measurement reports.

Real particles are rarely perfect spheres, so every method reduces each particle to an equivalent diameter. ISO 9276-2:2014, the standard for calculating mean sizes and moments from a distribution, takes the equivalent diameter of a particle of any shape as its size. The ISO confirmed the standard in 2025.

The equivalent-diameter convention explains most of the confusion around particle sizing. A sieve sorts particles by their width. A laser diffraction instrument reports the diameter of a sphere that scatters light the same way. An image analyzer can report length, width, or the diameter of a circle with the same projected area. Each answer is valid for its own definition of size.

Difference between Ensemble and Counting Methods

Particle sizing methods fall into two families. Ensemble methods read a signal from many particles at once and calculate the distribution that best explains it. Counting methods measure particles individually and build the distribution from the tally. The split shapes speed, sample size, and what a lab can say about particle shape.

1. Laser Diffraction

Laser diffraction is the workhorse of industrial particle sizing. ISO 13320:2020 applies to particles from approximately 0.1 µm to 3 mm in powders, sprays, aerosols, suspensions, emulsions, and gas bubbles in liquids. The standard notes that its optical model assumes spherical particles. Instrument software converts the scattering pattern into a volume-based distribution using Mie theory or the Fraunhofer approximation. Mie theory requires the sample’s refractive index, which laboratories often need from the requester.

2. Dynamic Light Scattering (DLS)

DLS covers the nanoscale end of the range. ISO 22412:2025 applies the technique to average hydrodynamic size and to size distributions of mainly submicrometre particles, emulsions, and fine bubbles in liquids. Instruments track how fast particles diffuse, then convert that rate to size through the Stokes–Einstein equation. The hydrodynamic diameter includes the solvent layer that moves with each particle, so it runs slightly larger than the physical core.

3. Analytical Sieving

Sieving remains the reference method for coarse powders and granules. The harmonized USP <786> states that sieving sorts particles mainly by their intermediate dimension and works best where most particles exceed about 75 µm. The chapter directs analysts toward an alternative method when material does not pass the sieves readily or when work moves below 75 µm.

4. Image Analysis

Image analysis is the one family that reports shape alongside size. ISO 13322-1:2014 covers static systems, where particles sit fixed on a slide or stub. ISO 13322-2:2021 covers dynamic systems and notes that they can measure far more particles than static setups. Count matters: ISO 13322-1 states that the distribution type and width strongly affect how many particles a lab must measure to reach a target accuracy. Contract Laboratory’s microscopy and imaging category lists providers for this work.

How Do Labs Report a Particle Size Distribution?

Most PSD reports lead with three percentiles: D10, D50, and D90. Each value is a particle size, not a percentage. D10 is the size below which 10% of the sample falls, D50 marks the median, and D90 marks the size below which 90% falls. The Islam et al. study notes that these percentiles can be expressed by number, volume, or mass, and that the basis changes the picture. Fines dominate a number distribution, while large particles dominate a volume or mass distribution.

The mean needs a qualifier. ISO 9276-2:2014 sets out two notation systems, the method of moments and the moment-ratio method, for calculating mean sizes from a distribution. Its scope also states that a report must name the measurement technique because sizing results depend on the measurement principle. A “mean particle size” with no basis or method attached tells a reader little.

Which Standards Govern Particle Sizing?

International standards and pharmacopeial chapters set the method expectations behind most particle size requests. ISO Technical Committee 24, Subcommittee 4 (particle characterization) maintains the core ISO series. The US, European, and Japanese pharmacopeias harmonize the main pharmaceutical chapters through the Pharmacopeial Discussion Group.

ISO 22412:2025 Expands DLS Options

The 2025 DLS revision is the most significant change since the original article ran. According to the published edition, the third edition adds multi-angle dynamic light scattering (MADLS) and imaging DLS. It also adds polarization-separated backscatter cross-correlation and extends the annex on online measurements. Labs that cite ISO 22412 in quotes or reports may need to update the edition they reference.

USP <429> Revision in Progress

The laser diffraction chapter is undergoing harmonization. A Pharmacopeial Forum proposal would retitle it “Particle Size Analysis by Laser Light Diffraction.” The proposal renames “Control of Instrument” as “Instrument Qualification” and substantially revises that section. It also clarifies scope and acceptance criteria for procedure development. Requesters working under USP methods can confirm which version their lab applies.

Sieving Interchangeability across Regions

Sieving carries regulatory reciprocity. Under ICH Q4B Annex 12, the ICH recommends the sieving chapters of the European, Japanese, and U.S. pharmacopeias be treated as interchangeable within ICH regions. USP adopted a revised harmonized <786> that became official with USP-NF 2023, adding the 75-mm sieve to the text.

Why Do Results From Different Methods Disagree?

Two accurate instruments can report different D-values for the same powder. The gap comes from three sources: how each method defines size, how the lab disperses the sample, and how many particles the measurement captures.

1. Shape and Size Definition

Shape drives most method-to-method differences. ISO 13320:2020 states that for nonspherical particles, laser diffraction yields a different distribution than sedimentation or sieving. The Islam et al. study quantified the effect on laser powder bed fusion powders screened at 45 µm. Laser diffraction put the D90 near 50 µm, imaging put it near 46 µm, and sieve analysis placed the D99.9 at about 45 µm. The authors attributed the laser results to satellites and agglomerates that skew light scattering.

2. Dispersion and Sample Preparation

Dispersion conditions can move results as much as the instrument. In the Islam et al. comparison, dry laser diffraction drastically overestimated the PSD of two hot isostatic pressing powders because agglomerates passed through the beam intact. Wet dispersion broke those agglomerates apart. For one of those powders, D90 values across techniques spread by roughly ±42% around the mean.

3. Sample Size and Statistics

The number of particles measured sets the confidence in the tails of the distribution. The same study estimated that static imaging measures roughly 10⁴ to 10⁵ particles per run, while sieving measures roughly 10⁷ to 10⁹. Missing a few coarse particles in a small static imaging sample can understate the D90 sharply.

The authors’ conclusion carries a practical point for purchasers and suppliers. When the two parties use different instruments or techniques, they need to understand the inherent bias between them before setting a specification. Contract Laboratory’s physical testing and materials evaluation and testing categories list labs that run several sizing methods side by side.

Where Particle Size Matters Most

Particle size shapes how a material flows, packs, dissolves, reacts, and looks. The weight each industry places on it depends on the product and its regulator.

Pharmaceutical Specifications

Drug developers face the most formal expectations. The decision tree for drug substance particle size in ICH Q6A asks whether particle size is critical to dissolution, solubility, bioavailability, processability, stability, content uniformity, or appearance. A “yes” to any of those questions leads to an acceptance criterion. The tree exempts solution dosage forms, since the drug substance dissolves completely.

Nasal and inhaled suspensions add another layer. Contract Laboratory’s nasal spray testing guide notes that suspension sprays require drug particle size distribution by cascade impactor, because drug particle size, not droplet size, governs absorption.

Metal Powders and Additive Manufacturing

Powder bed fusion depends on predictable spreading. The Islam et al. study notes that additive manufacturing calls for highly spherical powder with controlled flowability and packing density. It also reports that repeated powder recycling can shift the PSD and reduce circularity, which can affect part quality. Those findings make PSD a recurring release and reuse test rather than a one-time check.

What Labs Need and Requesters Look For

A particle size result is only as comparable as the information behind it. The standards above, and the method-comparison research, point to the details that make a request specific and a report usable.

1. Method, Basis, and Specification

A request that names the method and reporting basis lets a lab quote the right work. ISO 9276-2:2014 treats the measurement technique as an essential part of any reported result. Requesters can state whether the specification calls for laser diffraction, sieving, DLS, or image analysis, and whether results should be reported by volume, number, or mass. A specification written against one method rarely transfers cleanly to another. The Islam et al. study concluded that specifications and test methods should align with production controls, with any bias between methods established and understood.

2. Sample Information and Dispersion

Laser diffraction labs typically ask for the material’s composition and, for Mie calculations, its refractive index. Dispersion choices carry equal weight: Dry or wet, the dispersant, any surfactant, and sonication or air pressure. ISO 13322-1:2014 describes subsampling, dispersion, and particle presentation as vital to accuracy and points to ISO 14488 for sampling and ISO 14887 for dispersion. A known agglomeration tendency, solubility, or moisture sensitivity also belongs in the request.

3. Accreditation and Data Integrity

Many requesters ask for ISO/IEC 17025:2017 accreditation. Accreditation covers a defined scope, so a lab accredited for laser diffraction under ISO 13320 may not hold the same status for DLS or image analysis. Pharmaceutical work often adds GMP compliance, method validation, and USP or Ph. Eur. method references. Requesters can compare each provider’s scope against the standards their specification names.

For Labs and CROs

Particle size requests reach labs from pharmaceutical developers, powder metallurgists, coatings formulators, and food manufacturers. Labs that run laser diffraction, DLS, sieving, or image analysis, especially several methods under one roof, can review open projects in the Lab Requests section. The physical testing and microscopy and imaging categories collect related work. Labs updating method citations to ISO 22412:2025 can reflect that edition in their profiles and quotes.

Connect on Contract Laboratory

Contract Laboratory connects pharmaceutical developers, manufacturers, engineers, and researchers with laboratories that perform laser diffraction, dynamic light scattering, analytical sieving, image analysis, and related particle characterization.

• Submit a Request to describe a material, a sizing method, or a standard you need performed.
• View Requests to see open projects, including particle size and materials testing work.
• Register Your Lab to receive matched requests in your areas of capability.

This article was created with the assistance of Generative AI and has undergone editorial review before publishing.

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