Particle-size and powder methods help connect material attributes to drug-product performance and processability.
This decision-focused guide explains the scientific measurement basis, when to use it, its limitations, sample amount considerations, competing methods, FDA-facing concerns, and common mistakes.
Particle-size analysis measures the distribution of particle dimensions. Laser diffraction reports volume-equivalent spherical diameter distributions; microscopy and image analysis add shape, agglomeration, habit, and particle-identity context.
Use it when particle size affects dissolution, inhalation or suspension performance, blend uniformity, filtration, drying, flow, compaction, coating, lot comparability, or cGMP release specifications.
Laser diffraction assumes optical and shape models and can be sensitive to dispersion, refractive index, agglomerates, bubbles, obscuration, and sample preparation. It does not identify polymorph or chemistry by itself.
Amount depends on dry/wet dispersion, concentration, replicate number, and method validation. The Triclinic particle-size page lists instrument ranges rather than fixed sample amounts; sample needs should be scoped for each product and method.
Optical microscopy, static image analysis, SEM, BET specific surface area, powder flow, XRPD, Raman, and dissolution testing can compete or complement particle-size analysis depending on whether size, shape, chemistry, form, or performance is the decision driver.
FDA cares whether the particle-size method controls a clinically or manufacturably relevant attribute, whether dispersion conditions are justified, and whether validation covers specificity, precision, robustness, and the intended sample matrix.
Common mistakes include reporting only D50, missing multimodality, breaking or creating agglomerates during prep, choosing the wrong refractive index, ignoring morphology, and assuming particle size explains dissolution without checking form and residual solids.
Triclinic uses particle-size and powder-characterization methods to support real-world decisions about milling, micronization, agglomeration, blending, dissolution, stability, and release specifications. The work is applied when particle size or distribution shape may affect manufacturability, bioavailability, content uniformity, filtration, handling, or lot comparability, and when the method must be appropriate for the material rather than simply reporting a number.
The table below lists the specific platforms, brands, models, software, detectors, and capability notes relevant to this service area.
| Instrument or platform | Brand, model, software, or detector | Additional capabilities and use |
|---|---|---|
| Laser diffraction PSD | Malvern Mastersizer 3000 v.3.70 with Malvern Access Configurator v.2.20 | Particle-size distribution by volume-equivalent sphere diameter; dry range 0.1-3500 um and wet range 0.01-1400 um. |
| cGMP PSD methods | Malvern Mastersizer 3000 platform with method-development, verification, transfer, validation, and release-testing workflows | Validated particle-size methods, batch release results, and cGMP/non-GMP comparability studies. |
| Morphologically directed Raman support | Renishaw inVia / Thermo FT-Raman / Ondax low-frequency Raman platforms; 785 nm, 1064 nm, and THz-Raman options | Particle-level chemistry and morphology correlation, MDRS-style component identification, and composition of selected particle populations. |
| Powder flow | Hall FlowMeter AS-300 | Flow-rate and apparent-density measurements for powders where PSD affects processability. |
| Optical and digital morphology | Leica M80, Leica DM2500P, Keyence VHX-2000E, and Pax-it2! v.1.4.3 software | Particle-shape, agglomeration, habit, and topography observations to complement laser diffraction. |
| SEM/EDX morphology | Thermo Phenom XL SEM/EDX and FEI Quanta 3D FEG | High-resolution particle morphology and elemental confirmation for particles, contaminants, and agglomerates. |
This example shows how particle-size distribution data should be interpreted as a distribution, not a single number. The legacy particle-size page describes laser diffraction as a method in which a dispersed sample scatters light at angles related to particle size. The resulting distribution can support wet or dry method development, cGMP release testing, method verification, method transfer, and troubleshooting when particle size affects performance or processability.
These examples include technical resources, regulatory guidances, or literature relevant to the technique. Download buttons are placed at the bottom-left of each example.
Author: Melanie Bevill, Chris Seadeek, Nico Setiawan, Shawn Comella, Blaise Mibeck, and Steef Boerrigter
Publication date: November 2023
Abstract: This Triclinic application note links solid-form screening and selection to crystallinity, stability, solubility, hygroscopicity, manufacturability, regulatory needs, and IP objectives. It supports choosing analytical techniques based on the development decision rather than a fixed instrument list.
Author: International Council for Harmonisation / FDA
Publication date: 2024
Abstract: FDA notes that ICH Q2(R2) and Q14 describe validation and development principles for analytical procedures used to assess drug substance and drug product quality. These guidances frame FDA expectations for specificity, accuracy, precision, range, robustness, lifecycle management, and fit-for-purpose method evidence.
Author: Triclinic Labs
Publication date: 2019
Abstract: This white paper describes how low-frequency Raman can distinguish polymorphic forms using lattice-mode information not always available in conventional mid-frequency Raman. It supports using Raman as an orthogonal solid-form tool when XRPD, DSC, or FTIR are inconclusive.
Use this technique when its evidence better matches the sample, matrix, or development decision.
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Tell Triclinic what sample you have, what decision the data must support, what prior data are available, and whether cGMP, release, validation, or regulatory documentation is required.
