Fenofibrate API and particle size: why micronisation is a formulation question

How particle-size distribution affects your dissolution profile — and what to specify.

Fenofibrate is a poorly water-soluble molecule, and for a poorly soluble API the specification line that decides your dissolution profile is not assay — it is particle size. Two lots that pass the same identity and assay tests can behave very differently in the dissolution vessel, and the difference is often granulometry.

What Fenofibrate is used for

Fenofibrate is a lipid-regulating agent formulated for hypercholesterolaemia and hypertriglyceridaemia, usually as oral solids such as tablets and capsules. Because it is a BCS Class II compound — high permeability, low solubility — its absorption is dissolution-limited, which is precisely why the physical form of the powder matters so much.

For a formulator, that means the therapeutic performance you are designing for is tied to a physical attribute of the incoming material, not only its chemical purity. A lot that is chemically perfect but coarser than your method assumes can still miss your dissolution specification.

Particle size is a specification, not a preference

Micronised and non-micronised Fenofibrate are effectively different starting materials for your process. If your formulation and its bioequivalence data were built on micronised material, ordering a coarser grade is a formulation change, not a substitution, and your QA team will treat it as one.

Specify the particle-size distribution you need, ideally as D10, D50 and D90 values with the measurement method named, rather than asking for “micronised” and hoping the supplier’s definition matches yours. The word micronised alone is not a specification, because different suppliers cut it at different distributions.

Grade differences and monograph considerations

Pharmacopoeial monographs control identity, assay and impurities, but particle size is frequently held in an in-house specification layered on top of the compendial grade. Confirm both: which monograph the material is released against, and what PSD limits sit alongside it.

For a BCS Class II API, the particle-size distribution is part of the specification, not a preference you can leave to the supplier.

Ask whether the PSD is a controlled release parameter or merely a typical value reported for information. A number that appears on the CoA as “typical” is not the same as a number the supplier commits to hold batch to batch, and only the latter protects your dissolution profile.

Packaging, storage and handling in practice

Micronised powders are fine, low-density and prone to picking up static and moisture, so packaging and handling deserve attention at enquiry stage. Confirm the pack sizes, the liner configuration and any inert-gas or desiccant provisions, and agree them in writing before despatch.

If your warehouse decants into smaller quantities, flag it early. Repacking a micronised powder adds a handling step that can affect flow and introduces a documentation burden your QA team has to carry.

Documentation to request before the first PO

A batch Certificate of Analysis showing the PSD result, the particle-size method, the method of analysis, an MSDS and the product specification should be available before you order. DMF and open-part documentation should be available on request where your filing needs it.

Check that the CoA actually reports the D-values against stated limits, not just a pass statement. For this molecule, a CoA that omits the particle-size result is missing the one number most likely to explain a dissolution failure later.

A short checklist before you commit

• Specify the required particle-size distribution as D10, D50 and D90 with the method named.
• Confirm whether PSD is a controlled release limit or a typical reported value.
• Ask which monograph the material is released against.
• Agree pack size, liner configuration and any desiccant provision in writing.
• Request a batch CoA that reports the actual PSD result before raising the PO.