Palmitoylethanolamide (PEA, CAS 544-31-0) is sold as “micronized” and “ultramicronized” powder. Buyers reasonably assume these are graded terms with agreed limits. They are not.
Neither term has a pharmacopoeial definition, an ISO definition, or an industry-wide specification for PEA. Two suppliers can both write “ultramicronized” on a specification sheet and ship materials with materially different particle size distributions. For a poorly water-soluble fatty acid amide, that difference changes dissolution behaviour, bulk density, flowability and capsule-fill consistency, so it is not a labelling detail.
This note sets out where the commonly quoted numbers come from, what we measure on our own material, and which fields to ask for on a Certificate of Analysis so that a comparison between two suppliers is actually a comparison.
Where the commonly quoted figures come from
The particle size profiles most often repeated for micronized and ultramicronized PEA originate from a worked example in a published patent (US 8,663,701, Table I), which tabulated two materials produced by air-jet milling:
| Cumulative undersize | Micronized example | Ultramicronized example |
|---|---|---|
| below 14 µm | traces | absent |
| below 10 µm | about 96% | 100% |
| below 6 µm | 80% | 99.9% |
| below 2 µm | not indicated | 59.6% |
| below 1 µm | not indicated | 14.7% |
| below 0.6 µm | not indicated | 2.0% |
These are the figures of specific example materials, not a standard. A patent example describes what its authors made. It does not create a threshold that the industry has agreed to apply, and no standards body has adopted one since.
The single threshold most often carried over into commercial use is “more than 90% below 6 µm.” When a supplier writes “ultramicronized” without qualification, that is usually the criterion being invoked, but it is worth confirming, because the finer end of the distribution varies widely between materials that all satisfy the 6 µm threshold.
What we measure
Our ultramicronized PEA grade is produced by air-jet milling and the distribution is determined by laser diffraction with dry dispersion, per ISO 13320 (equivalently GB/T 19077-2016). Values below are for batch PEA-260505:
| Parameter | Value |
|---|---|
| D10 | 1.395 µm |
| D50 | 2.580 µm |
| D90 | 4.773 µm |
| D97 | 6.363 µm |
| D[4,3] volume mean | 3.04 µm |
| distribution mode | 2.55 µm |
Expressed as cumulative undersize, for direct comparison with any supplier’s figures:
| Cumulative undersize | This batch |
|---|---|
| below 14 µm | 100.0% |
| below 10 µm | 99.8% |
| below 6 µm | 96.7% |
| below 2 µm | 32.8% |
| below 1 µm | 3.0% |
| below 0.6 µm | 0.2% |
The material satisfies the “more than 90% below 6 µm” criterion with margin. It is coarser in the sub-2 µm fraction than the ultramicronized example tabulated above. Both statements are true at once, which is precisely why the adjective alone is not a specification. Distribution data is measured and reported per lot on the Certificate of Analysis.
Mesh is not a substitute for microns
Chinese powder-processing practice often designates ultrafine milled material by mesh, and “2000 mesh” is a common shorthand. It is a shop-floor descriptor, not a sieve specification: standard sieve series under ASTM E11 and ISO 3310 do not extend to that fineness, and there is no agreed conversion between a mesh number in that range and a micron value. A specification written only in mesh cannot be verified by a receiving laboratory. Ask for D10/D50/D90 in micrometres and the method used to obtain them.
What to ask for on the COA
- D10, D50 and D90 in micrometres, because a single median is not a distribution.
- D[4,3] or D[3,2], and the distribution mode.
- Cumulative undersize at the thresholds relevant to your specification, commonly below 6 µm, and below 2 µm where the fine fraction matters.
- Method and standard, such as laser diffraction per ISO 13320, or the alternative used.
- Dispersion mode, dry or wet; results are not interchangeable between them, and for a waxy amide the choice affects the result.
- Optical model, Fraunhofer or Mie, and refractive index if Mie.
- Whether the figure is a batch result or a release specification, and what the release limit is.
The seventh point is the one most often missed. A supplier can quote an excellent batch result while holding a release specification loose enough to permit a much coarser lot. Ask for the limit, not only the certificate.
Why the fine fraction is not free
Pushing a fatty acid amide finer is not simply a matter of milling longer. PEA is waxy and prone to agglomeration, and mechanical mills heat the material, which promotes the aggregation that the milling is meant to undo. Air-jet milling avoids the heating problem, but finer grades still cost throughput, and very fine powders bring their own handling consequences, including lower bulk density, poorer flow, greater electrostatic charging and different capsule-fill behaviour. A finer grade is not automatically the better grade for a given dosage form. Match the distribution to the format.
Specification summary
| Material | Palmitoylethanolamide (PEA) |
|---|---|
| CAS number | 544-31-0 |
| Molecular formula | C18H37NO2 |
| Molecular weight | 299.49 g/mol |
| InChIKey | HXYVTAGFYLMHSO-UHFFFAOYSA-N |
| PubChem CID | 4671 |
| Assay | 99% minimum by HPLC |
| Particle size method | Laser diffraction, dry dispersion, ISO 13320 / GB/T 19077-2016 |
| Production route | Organic synthesis, amidation of palmitic acid with ethanolamine; air-jet milled |
| Packaging | 25 kg per drum |
Review the PEA product page or read the PEA particle engineering buyer review for formulation-file routing.
This note is written for B2B raw-material evaluation. It describes physical and analytical properties of a raw material. It makes no health, therapeutic or cosmetic claim, and nothing here should be read as a statement about what any finished product does. Buyers are responsible for the claims made on their own labels and for confirming what is permitted in their market of sale.
Reference: US Patent 8,663,701, “Compositions containing ultra-micronized palmitoyl-ethanolamide,” Table I, cited here solely as the published origin of the particle size figures in circulation.