Power Ultrasound and the Production of Mesoscopic Particles and Aqueous Dispersions - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Power Ultrasound and the Production of Mesoscopic Particles and Aqueous Dispersions
The authors discuss advanced sonocrystallization particle-engineering techniques for manufacturing mesoscopic particles.

Pharmaceutical Technology

Productivity and flow rate

Particle size can be fine-tuned by varying the feed-solution flow rate. The particle size can be decreased by slowing down the feed-solution flow rate at a given solute concentration. Similarly, the particle size can increased by speeding up the feed-solution flow rate. Although the particle size can be tuned by adjusting the feed-solution rate, the corresponding gas pressure has a significant effect on the resulting particles (see Figure 5). This feature is important in using SAX for morphology control.


Temperature plays a major role in the SAX technology. It mainly influences the evaporation rate of the solvent employed in the process. Ultimately, it governs the particle size of the drug. Although particle size is the key parameter affected by temperature, thermal effects can influence the amorphous or crystalline character of the particle. This idea is of paramount importance when nonsolvent temperature is selected.

Ultrasound and nonsolvent

Power ultrasound and the selection of the appropriate nonsolvent are the keys to collecting concentrated droplets and inducing ultrasound-assisted nucleation. Applying ultrasound delivers astonishing results in terms of particle shape (see Figure 6). However, the choice of solvent has an equal effect on the resulting particles. SAX technology in general has shown potential in morphology control. It helps to generate the targeted particles and engineer them to the requirements of their ultimate end use.

Industrial scale

Useful scale-up equipment for ultrasonic processing has become available during the past 15 years. Probe-based systems generally have inherent problems associated with cavitational damage and inefficient power consumption. Adapting such systems for the pharmaceutical industry is difficult because they must be approved for use with flammable solvents—an essential feature of equipment for manufacturing fine chemicals and APIs.

Prosonix has designed its piezoelectric-based Prosonitron equipment to allow focused distribution of acoustic energy into a liquid by using several low-power transducers (21 in a 5-L flow cell) bonded to the outside of a cylindrical duct, as shown in Figure 1, (7, 8, 23). A new cells with one row of seven transducers, (see Figure 2) was designed specifically for kilo-laboratory and pilot-plant use, either in recirculation or continuous mode.

The key feature of the Prosonitron design is that the most significant transient cavitation takes place in the center of the device. The equipment is modular and easily cleaned for production according to current good manufacturing practice. It also can be steam-sterilized and is therefore useful for the aseptic manufacture of antibiotics, for example.

For manufacturing operations, it is more usual to configure a small ultrasonic flow cell into a recirculation loop, as shown in Figures 1 and 2, with a larger and existing reactor, crystallizer, bioreactor, or fermenter.

It seems more sensible to use this retrofit option and to be able to wheel the ultrasonic module from vessel to vessel or plant to plant than to build larger ultrasonic reactors. This configuration can also be modified easily to incorporate a secondary feed stream of solute solution or antisolvent directly into the intense ultrasonic field. For techniques such as SAX, the Prosonitron is a key element in large-scale production equipment (see the left of Figure 3).


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Jim Miller Outsourcing Outlook Jim MillerOutside Looking In
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAdvances in Large-Scale Heterocyclic Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler New Era for Generic Drugs
Sean Milmo European Regulatory WatchSean MilmoTackling Drug Shortages
New Congress to Tackle Health Reform, Biomedical Innovation, Tax Policy
Combination Products Challenge Biopharma Manufacturers
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
Source: Pharmaceutical Technology,
Click here