CAVITATION TECHNOLOGY – A RAPID AND NOVEL WAY OF

GENERATING NANOMATERIALS AND NANOEMULSIONS

SIVAKUMAR MANICKAM

Professor of Chemical and Nanopharmaceutical Process Engineering,

Head of the Research Division – Manufacturing and Industrial Processes (MIP)

Director – Centre for Nanotechnology and Advanced Materials (CENTAM)

Faculty of Engineering, University of Nottingham (Malaysia Campus), Jalan Broga,

Semenyih, Malaysia; Email: Sivakumar.Manickam@nottingham.edu.my

It is estimated that by 2014 the global pharmaceutical industry will be worth over $ 910 billion and

formulations will occupy a good share of that. As an increasing number of newly developed drugs

are sparingly soluble in water and are often also insoluble in organic solvents, consequently the

formulation of these drugs is a major obstacle to their clinical applications. Owing to their extremely

low solubility, these drugs usually possess poor bioavailability. The immediate formulation then aims

for the reduction in the particle size of these drugs so that the specific surface area increases which

ultimately enhances the bioavailability. Common ways of solving this problem include the use of

solubilizers, cyclodextrins, and mixtures of solvents. But to overcome the shortcomings existing with

these strategies, alternative attempts have been made to formulate the drugs as nanoemulsions.

Continuous search is on to find out the techniques by which these nanoemulsions could be

generated and which can make positive differences over the conventional techniques. In recent

years, the advantages of cavitation for emulsification have gained prevalence due to its widespread

use in a variety of processes i.e. physical, chemical and biological. In particular in the pharmaceutical

applications, emulsions with the desired mean droplet size of less than 1 µm are essential in order to

ensure an enhanced bioavailability and high physical stability. Generation of nanoemulsions using

cavitation approach is highly energy efficient and also flexible control of droplet size are possible

over other conventional mechanical and high-pressure emulsification techniques.

Ultrasound bubble collapse and the generation of nanoemulsion

Highly intensive ultrasound supplies the power needed to disperse a liquid phase (dispersed phase)

in small droplets in a second phase (continuous phase). In the dispersing zone, the imploding

cavitation bubbles cause intensive shock waves in the surrounding liquid and result in the formation

of liquid jets of high liquid velocity. At appropriate energy density levels, ultrasound can well achieve

a mean droplet sizes well below 1 µm. Efficiently generating the emulsion property of ultrasonic

cavitation has been exploited for the preparation of a number of nanopharmaceutical emulsions as

well as suspensions incorporated with a wide variety of drugs/natural products that have intense

potential.

HR-SEM images of Curcumin nanoemulsion obtained using ultrasound cavitation

Nanoemulsion of Aspirin, Curcumin, Ganoderic acid and Polysachharide of Ganoderma (left to right)

It is very much anticipated that the immense potential of this simple cavitation process technology

employed in the generation of nanoemulsions will have direct impact and great promise for the

future of cosmetics, diagnostics, drug therapies and biotechnologies.

References

1. Manickam Sivakumar, Siah Ying Tang, and Tan Khang Wei, Cavitation Technology, A Greener Processing Technique for the generation of Pharmaceutical Nanoemulsions, Ultrasonics Sonochemistry, 21(6), 2069-2083, 2014.

2. Siah Ying Tang, Shridharan Parthasarathy and Manickam Sivakumar, Impact of Process Parameters in the Generation of Novel Aspirin Nanoemulsions – Comparative studies between Ultrasound Cavitation and Microfluidiser, Ultrasonics Sonochemistry, 20(1), 485-497, 2013.

3. Siah Ying Tang, Manickam Sivakumar and Nashiru Billa, Impact of Gelling, Emulsifiers and Osmotic Pressure in the generation of highly stable Single Core Water-in-Oil-in-Water (W/O/W) Nano Multiple Emulsions of Aspirin assisted by Two-stage Ultrasonic Cavitational Emulsification, Colloids and Surfaces B: Biointerfaces, 102, 653-658, 2013.

4. Siah Ying Tang, Manickam Sivakumar, Angela Min-Hwei Ng and Parthasarathy Shridharan, Anti-inflammatory and Analgesic activity of novel oral Aspirin-loaded Nanoemulsion and Nano multiple emulsion formulations generated using Ultrasound Cavitation, International Journal of Pharmaceutics 430, 299-306, 2012.

5. Noosheen Zahid, Asgar Ali, Manickam Sivakumar and Siddiqui Yasmeen and M. Maqbool, Potential of Chitosan loaded Nanoemulsions to control different Colletotrichum spp. and maintain quality of tropical fruits during cold storage, Journal of Applied Microbiology, 113(4), 925-939, 2012.

6. Siah Ying Tang and Manickam Sivakumar, Development of A Novel, Facile and Controlled Technique to Produce Submicron Multiple Emulsions of Ferrous Fumarate using Liquid Whistle Hydrodynamic Cavitation Reactor, American Institute of Chemical Engineering Journal (AIChEJ) (In Press)

7. Siah Ying Tang, Manickam Sivakumar, Tan Khang Wei and Nashiru Billa, Formulation Development and Optimization of a Novel Cremophore EL-based Nanoemulsion using Ultrasound Cavitation, Ultrason. Sonochem., 19(2), 330-45 (2012).

8. Tan Khang Wei and Manickam Sivakumar, Response Surface Methodology, an Effective Strategy in the Optimisation of the preparation of Curcumin-loaded Nanoemulsion, Asia-Pacific Journal of Chemical Engineering, 7(S1), S125-S133, 2012.

9. Siah Ying Tang and Manickam Sivakumar, Design and Evaluation of Aspirin-loaded Water-in-Oil-Water Nano Multiple Emulsions prepared using Two-step Ultrasonic Cavitational Emulsification Technique, Asia-Pacific Journal of Chemical Engineering 7(S1), S145-S156, 2012.