The guaranteed way to avoid dissolution is to centrifuge or filter your sample and use the clear supernatant as diluant. This method is only practical if you have a small volume sample cell. An alternative is to unplug the circulation and use a couple of syringes to flush the measurement cell with diluted sample. I don't know how practical this is with a Mastersizer 3000, though.

Ada Chang

I assume your API is in powdered form. Please confirm. You also do not indicate the accessory you're using with the Mastersizer 3000..

It is never advisable to measure any material in saturated solution. We do not recommend this for a number of reasons:

• Adding powered material to a saturated solution promotes crystallization ('seeding')
• The refractive index of a saturated solution is close to that of the solid and thus optical contrast is low
• The thesis is always ’but my small material will dissolve first and affect the PSD’. I have never seen any indications of this from looking at the x10, x50, and x90 values. And, of course, in a volume/mass distribution this effect is probably not seen in relation to dispersion

Also note that it needs a 2% change in surface area to make a 1% change in diameter and that solubility produces little change in PSD, typically. A sparingly soluble material is usually superb to measure as limited solubility aids dispersion.

If you can't measure the material dry or in another liquid, then the advice is to add wetted solid to the accessory and keep adding until the obscuration is reasonably high and relatively constant - one can keep measuring and monitoring at the same time (and I'm sure that changes will be minimal). In effect this is making a concentrated solution in situ rather than separately and this is always preferable as supersaturation is avoided. I have a number of published examples of materials such as calcium sulfate where measurement at higher obscuration in water is identical to that in (expensive) alcohols such as IPA.

I bow to other Alan's greater experience. Do what he said.

Alan Parker

Thank you for your generous comment! How’s the consultancy business going?

Alan F Rawle Thanks for the information! The API is in powdered form and I am using the Hydro MV.

Ada Chang

Thank you for your response. These days it seems that many questioners simply do not acknowledge any response. For example:

https://www.researchgate.net/post/What_might_be_the_reason_of_getting_just_one_peak_while_measuring_Particle_size_and_Zeta_Potential_using_zeta_sizer

https://www.researchgate.net/post/DLS_How_to_convert_Number_Intensity_and_Volume_to_q3_q6_or_q0_distributions

https://www.researchgate.net/post/How_to_determine_the_refractive_and_absorption_index_of_any_nanoparticle_dispersion_for_PSD-measurements

See the discussion:

https://www.researchgate.net/post/People_asking_questions_here_on_researchgate_often_do_not_feed_back_to_answers_at_all2

Alan F Rawle

I had a follow up question if you don’t mind! You mentioned that a sparingly soluble material is actually ideal for measuring particle size—are there limits to the solubility of the material that we should stick to? Right now, we’re seeing approximately 0.2-2mg/mL dissolved in initial solubility tests.

Thanks again for your help with supersaturated solutions. I believe we were seeing that crystallization as samples sat for longer than a few minutes before measurement, so we’re moving away from that idea going forward!