Dear VE

The answer to this question depends on the type of particles being sonicated. In general, sonication can be used to reduce particle size, but it can also be used to increase particle size. For example, sonication can be used to break down large particles into smaller ones, or to agglomerate smaller particles into larger ones. In the case of agglomeration, increasing the sonication time can result in larger particles. However, if the particles are already at their smallest size, increasing the sonication time will not result in larger particles.

The equation that relates sonication time to particle size is the following:

Particle size = (sonication time)^(-1/3)

This equation shows that as the sonication time increases, the particle size decreases. Therefore, if the particles are already at their smallest size, increasing the sonication time will not result in larger particles.

@Sagayaraj thanks for your answer. The nanoparticles were formed by nanoprecipitation from pegylated PLGA. I am aiming for a size between 100nm-200nm in the blanks before drug loading.

Dear VE

Nanoprecipitation is a process in which a polymer solution is mixed with a non-solvent, causing the polymer to precipitate out of the solution in the form of nanoparticles. The size of the nanoparticles can be controlled by adjusting the concentration of the polymer solution and the rate of addition of the non-solvent. By controlling these parameters, nanoparticles with a size between 100nm-200nm can be produced. Once the nanoparticles are formed, they can be loaded with drugs to create drug-loaded nanoparticles.

It may be that sonication is increasing the aggregation rate. This is usually limited by the diffusion rate of the particles (and their concentration). Any external energy that increases the velocity of the particles can increase the chances of particles approaching close enough for attraction to occur that is faster than would occur by diffusion alone.

Another example of this is shear-induced aggregation. i.e., dispersions that aggregate due to applied shear such as stirring.

(I use "aggregation" to include flocculation/agglomeration).

@John thanks for your thoughts. I appreciate it.

Victor Ejigah

You do not tell us anything about the system that you are sonicating or show the particle size distribution. Chemistry can be very important here. Increasing the sonication time or power increases the collision frequency between particles. If the particulate system is unstable (e.g. inadequate zeta potential in the case of charge/electrostatic stabilization) then recombination (aggregation/agglomeration) can occur. The increase in size will be expected as the attractive van der Waals forces will overcome inertial/separation forces. I've seen this occur with micron-sized calcium carbonate with a positive zeta potential. Time of sonication of 40 minutes is excessive and is disintegrating up your sonication tip or probe. If you don't believe me then try sonicating DI (18 MOhmcm-1) water and measuring the conductivity over that 40 minute period.

Also see (registration required):

Dispersion and nanotechnology

https://www.malvernpanalytical.com/en/learn/events-and-training/webinars/W190528DispNanoMat

Ultrasound, cavitation, and the singing kettle

https://www.malvernpanalytical.com/en/learn/events-and-training/webinars/W130619UltrasoundCavitationSingingKettle.html

Note, BTW, that particles of 200 nm would not be considered 'nano' by the international ISO and ASTM norms.

Vadim S. Gorshkov

Alan F Rawle Thanks for sharing your thoughts and the links. I am working with PLGA nanoparticles produced via nanoprecipitation. The procedure involved dropwise addition of organic phase containing polymer into the aqueous phase under sonication until the polymer solution was completely added to the aqueous phase. This took 30 minutes The size distribution of blanks ranged from 195-250nm. Further sonication led to increase in size 421 (another 20 minutes) and 505nm (an extra 20 minutes). From your contribution, this is excessive and I would have to reduce the sonication time which means faster addition of the polymer droplets into the aqueous phase. The organic phase is a co-solvent of acetone/ethyl acetate.

Victor Ejigah

If you're sonicating organic solvents rather than water, then most of the input energy is converted into boiling and volatilizing the solvent. Water is the most effective energy transfer liquid for ultrasound. You say you're adding organic to water - what's the finishing concentration range? What is meant by 'completely added'?

Alan F Rawle Thanks for your response. By completely added, I meant the polymer solution was added (to the aqueous phase) down to the last drop. The final concentration of polymer in solution is 0.4-0.6mg/ml.

Victor Ejigah OK, so it's around 4 - 6% w/v concentration. Mainly water then so energy transfer could be fine if it doesn't damage the polymer. See the second webinar above (registration required). Look at 25:50 onward.

Ultrasound, cavitation, and the singing kettle

https://www.malvernpanalytical.com/en/learn/events-and-training/webinars/W130619UltrasoundCavitationSingingKettle.html

Alan F Rawle Thanks a million.

Thankyou professors.