Ultrasound Assisted Processes

by
Dr. Sanjaykumar R. Patel
Chemical Engineering Department
S.V. National Institute of Technology, Surat
 Introduction
Ultrasound - sound waves at a frequency above the
threshold of human hearing (16Hz – 20,000Hz)

It can affect wide range of chemical and physical processs.

It has been used by chemist and chemical engineers for a

variety of areas as:

• to enhance filtration
• electrochemistry • to accelerate extraction
• food technology processes
• synthetic chemistry • crystallization
• Nanotechnology • emulsification
• sewage treatment • to enhance many
• dewatering and drying processes where
materials diffusion takes place
• Ultrasonic waves are generated by mechanical
vibrations of frequencies higher than 18 kHz.

• When these waves propagate into liquid media,

alternating compression and expansion cycles are
produced.

• During the expansion cycle, high intensity ultrasonic

waves make small bubbles grow in liquid.

• When they attain a volume at which they can no longer

absorb enough energy, they implode violently.

• This phenomenon is known as cavitation.

 The Cavitation phenomenon

• Sound waves travels through liquid

medium in the form of compression
and refraction phases

• Local pressure variation occurs

• During compression phase:

Liquid molecules are pressed together

• During refraction phase :

Liquid molecules are stretched apart

Developmentment and collapse of caviation • Cavitation occurs at the spots where

bubbles the vapor pressure in the liquid drops
well below it vapor pressure
• Each cavitation bubble collapse acts as a localised
"hotspot" generating temperatures of about 5,000 oC and
pressures in excess of 2000 atmospheres.

• This is the energy that is utilized to accelerate the rate of

a chemical reaction, create new reaction pathways or
even generate different products from those obtained
under conventional conditions .

• The occurrence of these special reactions in a cavity is

typically described as sonochemistry.
The relations among energy, pressure and
duration for sonochemistry and other
chemistry
 Types of Cavitation

• Acoustic cavitation
-the mechanical interaction between sound waves and
bubbles in liquids
• Hydrodynamic cavitation
-generated by throttling the liquid flow through a
constriction
• Optic cavitation
- photons of high intensity light (laser) rupturing the liquid
continuum.
• Particle cavitation
- beam of elementary particles like a neutron beam
rupturing a liquid
Acoustic Phenomena
 The Chemical and Physical Effects of
Ultrasound
• The chemical, physical and biological effects of cavitation
depend both on the type of cavity produced

1) stable cavity
- where the bubble pulsates about an equilibrium radius over
many acoustic cycles.

2) transient cavity
- where the bubble grows extensively over time-scales of the
order of the acoustic cycle, and then undergoes an energetic
collapse

Both of these factors depend strongly on the local sound field at

the bubble and on the sizes of bubble present in the population
 The Chemical effects

• Chemical effect of cavitations occurs in three

distinct regions:

– within the bubble itself which can be thought of as a

microreactor

– in the liquid region immediately adjacent to the bubble

where the temperature are not so great

– In the immediate vicinity of the bubble where the

shockwave produced on collapse will create enormous
shear forces.
 The Physical Effects

• The physical effects is responsible for

– improvement of mass transport from turbulent mixing

and acoustic streaming,

– the generation of surface damage at liquid-solid

interfaces by shock waves and microjets

– the generation of high-velocity interparticle collisions

in slurries,

– the fragmentation of friable solids to increase surface

area.
In heterogeneous liquid/liquid
reactions, cavitational collapse at or
near the interface will cause
disruption and mixing, resulting in
the formation of very fine emulsions
Cavitation bubble collapse in the liquid phase near to a
particle can force it into rapid motion. Under these
circumstances the general dispersive effect is accompanied
by interparticle collisions which can lead to erosion, surface
cleaning and wetting of the particles and particle size
reduction.
 Neck formation from localized melting The effect of ultrasonic irradiation on the
is caused by high-velocity interparticle surface morphology and particle size of
Ni powder
collisions.
 Ultrasound Sources

• The source of the ultrasound is a piezoelectric material (lead-

zirconate-titanate ceramic (PZT) or quartz) which is subjected to
high voltage alternating current with an ultrasonic frequency (15 kHz
– 10MHz).

• The piezoelectric material expands and contracts in this electric field

and is attached to the walls of the cleaning bath (or amplifying horn)
and converts electrical energy into sound energy

• There are three main designs

(a) ultrasonic cleaning bath
(b) cup horn sonicator
(c) direct immersion ultrasonic horn
 Ultrasonic horn
Frequecy – 22.7 kHz
Rated output – 120W,240W
surface area of 3.46 and 4.91 cm2

Ultrasonic bath
one can get these at different operating
frequencies,
variable power dissipation is possible

Ultrasonic horn and bath

Triple-frequency flow cell

capacity of 7.5 L
the total power dissipation is 900 W
when all the transducers with combination
of 20 + 30 + 50 kHz frequencies are functional
 Industrial Applications

• The different ways in which cavitation can be used beneficially in the

chemical processing applications:

(a) Reaction time reduction.

(b) Increase in the reaction yield.
(c) Use of less forcing conditions (temperature and pressure)
compared to the conventional routes.
(d) Reduction in the induction period of the desired reaction.
(e) Possible switching of the reaction pathways resulting in
increased selectivity.
(f) Increasing the effectiveness of the catalyst used in the reaction.
(g) Initiation of the chemical reaction due to generation of highly
reactive free radicals.
Ultrasound assisted filtration
Fouling
Use of ultrasound
Acoustic streamng
Microstreaming
Important Parameters
Ultrasound assisted membrane modules
 Ultrasound assisted crystallization
Crystallization
Crystallization is define as the solid-liquid separation techniques in which a solid phase is
separated from mother liquor or describing it technically there is a mass transfer of a solute
from the liquid solution to a pure solid crystalline phase.

Solution, Solubility and Supersaturation

26
Solubility Curve and MSZW
• Importance of solubility
The Solubilty Curve is essential for the design of crystallization
processesas it helps;

– To indicate the yield

– The type of crystallization to perform
– Method of supersaturation generation

• Importance of MSZW
• Knowledege of the MSZW can help in the optimum rate of
supersaturatuion generation to avoid excessive secondary
nucleation. It can help;

• indetify the seeding regime

• Indentify optimum supersaturation level
 Anti-solvent crystallization process

• The main driving force for precipitation is rapid and high supersaturation.
• The crucial crystal properties such as size, morphology and purity are
significantly dependent on the rate, magnitude and uniformity of
supersaturation generated during the process of crystallization
 Ultrasound assisted crystallization

• In conventional crystallization techniques, a solution

containing materials to be crystallized is super saturated
either by cooling or by evaporation and is then seeded.

• The problem with the seeding is that it may be initiated

non uniformly, so the crystal growth proceeding at
different rates at different nuclei sites.

• The resulting crystal may then show a very broad and

uneven crystal size distribution.

• It is also a considerable practical importance to be able

to control the onset of crystallization in large scale
production process.
 Benefit of cavitation in crystallization

• Easy primary nucleation in materials which are usually difficult

to nucleate narrowing the metastable zone width.

• Initiation of Secondary nucleation.

• the production of smaller, purer crystals that are more uniform

in size .

• Reduced agglomeration.

• Manipulation of crystal distribution by controlled nucleation.

 Antisolvent Crystallization of Drugs

• Approximately 40% of drugs in the industry are falling in the category of

•low
Antisolvent
solubility–high Crystallization
permeability (ClassofII),
permeability(Class IV).
Poorly
and low Water
solubility–low

Soluble Drugs
• These classes have the limited bioavailability of drugs due to their low
solubility and dissolution rate.

• The bioavailability is defined as the percentage of the quantity of the drug

absorbed compared to its initial quantity of dosage, which can be
improved by a decrease in their particle size.

• Also, the dissolution rate of the active pharmaceutical ingredient (API) is

proportional to the available surface area for dissolution.

• Nanoparticles can be obtained either by top-down approach or bottom-up

approach.
 Nanonization Techniques

Top down approach Bottom up approach

Jet milling Spray drying

Pearl mill
Spray freeze drying
Spiral media milling

High pressure Supercritical Fluid

homogenization Technology
These techniques are not efficient due
to high energy input and denaturation Anti-solvent crystallization
during the milling process
Anti-solvent precipitation (‘‘bottom up’’ approach)
is simple, cost effective, and easy to scale-up
Benefits:
(i) water can be used as an anti-solvent as it has a
low solubility toward most drug compounds
(ii) additional experimental parameters like;
ultrasonic waves can be applied through the
crystallization process.
Drawbacks of the process

• The technique involves dissolution, followed by precipitation and then

drying. Thus, the mechanical energy input is minimized but the resulting
nanoparticles might be crystalline or amorphous and also depending on
the process conditions.

• Poor micromixing during anti-solvent process leads to accidental zones

of local supersaturation and, therefore, aggregation of particles.

• Ultrasound proves to be a feasible mixing method to provide uniform

conditions throughout the vessel during anti-solvent process.
 ULTRASOUND ASSISTED ANTISOLVENT
CRYSTALLIZATION

• The use of ultrasonic waves in crystallization has been increased at

laboratory scale because;
– (i) rapid and uniform nucleation throughout the sonicated volume leads to
smaller and uniform-sized particles,
– (ii) reduction of agglomeration of particles and controlling the number of nuclei
.
• When ultrasound waves propagate through a liquid medium, its power will
initiate an important phenomenon known as cavitation.
• The power of ultrasound and cavitation phenomena will initiate the
nucleation and thereby crystal growth in a crystallization process.
• The use of ultrasound may also influence the solubility and thereby the
supersolubility.
• It can also alter the crystal habit as the ultrasound can increase or
decrease the growth rate of certain crystal faces.
 Important Parameters

The factors which of affects the particle size of drugs are;

ultrasound addition time,

ultrasonic power intensity,
the time at which the sonication is applied

-The particle size is mostly observed as to decrease with the increase in

ultrasonic power input. This phenomenon is attributed to the increase in
erosion effect on the surface of large crystals with an increase in
ultrasonic power and hence, crystal can agglomerate.
-The other parameter, sonication time is also responsible to decrease the
particle size to a certain extent.
-The most important effect of the presence of an ultrasonic wave during
crystallization is that it reduces both the nucleation induction time and the
metastable zone width.
Other factors which may affect the particle size in the
presence of ultrasound waves are;

• Drug Concentration
• Drug Solution Flow Rate
• Crystallization temperatures
• Solvent to Antisolvent (SAS) Volume Ratio
• Stirring Speed
 Laboratory Scale up

Liquid antisolvent precipitation

Antisolvent crystallization set up

 DETAILS OF ANTISOLVENT CRYSTALLIZATION OF
DIFFERENT APIs
API Parameters Particle Size (µm)
Carbamazepine Temperature: 25-45°C 13.9-112.3
Drug concentration :10-40 mg/ml
Flow rate: 1.4-10 ml/min
Sonication time: 30-90s
Meloxicam Solvent: DMF 0.183-0.750
Temperature: 8°C
Stabilizer concentration: 0.1-0.6%w/v
Sonication: 300 W for 20 time length

Nitrendipine Solvent: mixture of PEG 200 and acetone 0.2-0.218

(1:1 v/v)
Drug concentration: 30mg/ml
Stabilizer (PVA) concentration:
0.15%(w/v)
Temperature: 3°C
Stirring speed: 400 rpm
Sonication: 400 W, 15 min
 Sonocrystallization of lactose

Treatment of dairy wastewater to meet the environment regulations is very crucial

problem due to its high biological oxygen demand (BOD).

Whey contains 30,000 to 50,000 mg/L biochemical oxygen demand (BOD), which
is responsible for high polluting potential of whey.

The main cause of the BOD in dairy wastewater is due to the lactose content in
whey (dairy stream considered as waste).

The solution to this problem is a challenge for engineers to select a process with
combination of both economical and environmental acceptability.

It is reported (Bund and Pandit, 2007b) that recovery of lactose from whey solves
the problems of whey utilization and pollution reduction as lactose recovery itself
can reduce BOD of whey by more then 80%.

Therefore, the dairy industry must have to either decrease the lactose content
from whey or to recover huge amounts of lactose from whey before the disposal
into the environment.
 Sonocrystallization set-up

Operating conditions of ultrasound bath

Frequency : 20 KHz
Rated output power : 120 W
Dimensions of Bath :
15cm×15cm×14cm
Surface area of ultrasound : 225cm2
Irradiated face
Temperature : Room temperature (30±3°C)
Volume of the sample : 20 ml
Lactose solution : Reconstituted
Anti-solvents : Acetone or n-Propanol
Figure 3.1. Photograph of experimental set-up
 Parameters investigated

• Effect of solvent concentration (70-95% (v/v))

• Effect of time (2-8 min)
• Effect of lactose concentration (12-18 % w/v)
• Effect of pH (1-4)
• Time of stirring (4-32 min)

In order to develop an optimized sonocrystallization process for the recovery of

lactose from actual whey, it was necessary to check efficacy of sonocrystallization in
reconstituted lactose solutions with different pH (2.9±0.1 and 4.2±0.1) and protein (0.2 –
0.8% w/v) concentrations.

• Effect of protein concentration (0.2% - 0.8% (w/v)) and pH (2.9±0.1 and 4.2±0.1)
 Figure 1. Effect of time on sonicated and non-sonicated samples

90
Recovery of lactose
80
Sonicated samples:
Lactose recovery (%w/w)

70

85.26% (w/w) in 8 minutes

60

Without sonication:
50

Sonicated Samples
40 Non-Sonicated samples(stirred at 500 rpm) 46.69 % (w/w) in 8 minutes
85 (% v/v) acetone concentration
30
0 4 8 12 16 20 24 28 32 36
Time (min)

Higher recovery of lactose in sonicated samples in presence of an anti-solvent was

attributed to the cavitation which results in the occurrence of micro-streaming and
enhances heat and mass transfer
 Effect of lactose concentrations on crystal size distribution
Commercial lactose 12% lactose

50

40

Percentage crystals
30
14% lactose 16% lactose
20

10

0
0 2 4 6 8
Crystal diameter (micrometer)

Lactose 16% w/v Lactose 14% w/v Lactose 12% w/v

Narrower CSD in higher initial lactose concentration

Tomhawk shape Rod like shape

 Sonocrystallization kinetics

• The crystallization kinetics was studied using mixed suspension mixed

product recovery (MSMPR) model.

−L
n = n0 exp 
 G t 

Where, ‘n’ is the number of crystals per ml

‘n0’ is the number of embryo size crystals
‘L’ is the average crystal diameter (µm)
‘G’ is the crystal growth rate (µm/s)
‘t’ is the crystallization time (s)

The crystal growth rate (G) was calculated by plotting ln(n) vs. L.
 Lactose crystal diameter determination by Turbiscan

SRP 4 (25/02/09 18:56)

Back Scattering 0:00

Stokes law applies:
0:01
100% 0:02
0:03
V *18η
0:04
d=
80% 0:05
0:06
g * ∆Q
0:07
60% 0:08
0:09
0:10
40% 0:11
0:12
0:13
Where,
20%
0:14
0:15
d = diameter of the particle
0:16
0:17
V = particle migration velocity
0% 0:18 Ƞ = continuous phase viscosity
∆Q = density difference between two phases
0:19
0mm 20mm 40mm 60mm

Backscattering diagram for sample of 16% (w/w) lactose g = is the gravitational acceleration
solution, 80% (v/v) acetone concentration, 6 min sonication

Data of lactose crystals in acetone-water mixture

Temperature due to sonication Continuous phase (Acetone + Continuous phase (Acetone + Dispersed phase density
with respect to time 2-8 min in K Water) viscosity (cP) Water) density (g/cm3) (g/cm3) (Lactose)
307 0.6943 0.8240 1.54
308 0.6778 0.8229 1.54
309 0.6612 0.8218 1.54
310 0.6451 0.8206 1.54
 Sonocrystallization kinetics
16 16.4
y = -0.3059x + 19.841
16.2 R2 = 0.996
15.8 y = -0.0924x + 16.7
R2 = 0.8079
16
15.6
15.8

ln n
ln n

15.4
15.6

15.2 15.4

15.2
15

15
14.8 10 11 12 13 14 15 16
13 13.5 14 14.5 15 15.5 16 16.5 17 17.5 18
L (Micrometer)
L (Micrometers)

a c
19
18.5
18 y = -0.291x + 20.2
2
17.5 R = 0.9936

17 - 0.3059 = ( - 1 / G t)
16.5
ln n

16
15.5
15 G = Crystal growth rate
14.5
14 L = Crystal diameter
13.5
13 a t = Crystallization time
5 10 15 20
L (Micrometers)

b
Plots of L (diameter of crystals) vs. ln[n(number of crystals recovered/ml)] for the lactose recovered from
reconstituted solutions lactose content 16% w/v, (a) 80% (v/v) acetone concentration without sonication (b) 80% (v/v)
acetone concentration With sonication (c) 85% (v/v) propanol concentration with sonication
 Lactose Crystal growth rates

Crystals growth rate obtained for the samples at different conditions

Samples Crystallization Growth rate G

time (s) (µm/s)
80% (v/v) acetone 480 0.0022
concentration without
960 0.0011
sonication
1920 0.0006
80% (v/v) acetone 120 0.029
concentration with
240 0.014
sonication
360 0.010
480 0.007
 Mean value kinetics obtained by Turbiscan

8 min 8 min • BS* = 1/(λ)1/2

• λ = 2d / [3 Φ(1 - gs) Qs]

16 min
6 min Where,
4 min
λ = photon transport length (um)
2 min
d = particle diameter
Φ = particle volume fraction
32 min gs and Qs = optical parameters in
the theory of Lorenz–Mie.

a b
Delta backscattering mean value kinetics at 80% (v/v) acetone concentration,
(a) 8-32 min stirring time, (b) 2-8 min sonication time

Percentage backscattering decreases with increase in stirring time, which indicates that
size of crystals increases, while, In case of sonication, size of crystals are decreases
under continuous sonication with time

* Azema N, 2006. Sedimentation behaviour study by three optical methods - granulometric and electrophoresis measurements,
dispersion optical analyzer. Powder Technol, 165,133–139.
 Whey obtained from dairy

Whey with Whey after

fat content fat removal
 CSD and morphology of lactose by stirring
Tomahawk
shape
of crystals

60
50

P ercen tage crystals

40
30
20
10
0
0 2 4 6 8
Average crystal diameter (Micrometer)

1 h stirring 3 h stirring 1 h stirring, 3% w/w seeding

SEM of lactose recovered from whey

Spread of CSD was found to be affected
High level of agglomeration of lactose was observed by crystallization time and seeding
 Optimization of process parameters in the recovery of
lactose from whey by sonocrystallization using Taguchi
method.

Taguchi method

• Taguchi method utilizes a special set of arrays called orthogonal

arrays to study a large number of variables with a small number of
experiments and gives full information of all the parameters that
affect the performance.

• Taguchi method uses a statistical measure of performance called

‘signal-to-noise’ ratio, (S/N ratio), which converts the trial result data
into one value which reflects the amount of variation present in data.
 Higher is better (S/N)

S 1 n 1 
= − 10 log  ∑ 2 
N HB  n i yi 

• n is the repetition number of each experiment

• yi is the recovery of lactose at the ith test

Analysis of Variance

• After performing the statistical analysis of S/N ratio, analysis of variance

(ANOVA) is calculated for estimating error variance and to determine the
relative importance of various factors.

• From relative importance of factors and from the S/N ratio, the optimum
conditions of factors were chosen.
 Factors and their levels in the experimental design

Table 10. Factors and their levels in the experimental design

Level Factor A Factor B Factor C Factor D

(initial lactose (initial pH of (solvent concentration, (sonication time,
concentration, %w/w) sample) %v/v) minutes)
1 5 2.5 65 5

2 10 4.5 75 10

3 15 6.5 85 15
 Total S/N ratios
Table 12. Total S/N ratios (higher is better)

Factors
Levels A B C D

1 107.75 106.53 100.38 100.90

2 106.31 106.74 114.30 110.88
3 110.37 111.14 109.74 112.45

Optimized condition

initial pH of sample at level 3 : 6.5

initial lactose concentration at level 3: 15 (%w/w)
acetone concentration at level 2: 75 (%v/v)
sonication time at level 3: 15 (min)

Percentage recovery at optimized condition : 89.03 %w/w

 Morphology by sonocrystallization

B
A

Figure 8. SEM of (A) conventional lactose sample (B) lactose

recovered from whey at optimized conditions

Tomahawk shape Rod/needle like shape

 Conclusions
• Lactose recovery by sonocrystallization led to early crystallization of lactose
with 83.01% w/w recovery as compared to recovery by non-sonicated
(mechanically stirred) samples was only 38.96% w/w at the end of 4 min.

• Therefore, the enhancement in the percentage lactose recovery was found

44.05% in sonocrystallization.

• The rapid crystallization proposed in the presence of ultrasonic waves was

due to rapid mixing of the anti-solvent with the lactose solution, which leads
to rapid precipitation of lactose.

• Cavitation events, such as micro-streaming and acoustic-streaming, with

extremely localized temperature and pressure, within the mixture of anti-
solvent and lactose solution caused early nucleation, which was responsible
for higher recovery of lactose.
 Wastewater Treatment
• ultrasound has been extensively used as an advanced
oxidation process (AOP) for waste water treatment.

• When ultrasound is applied to effluent, water undergoes

thermal dissociation to H atoms and OH radicals.

• OH is highly reactive and can oxidise almost all

contaminants in water.

• This primary oxidation is the reason for the degradation

of contaminants in water.
 Method and mechanism
• The generation of oxidative species is an effect of
cavitational collapse.

• During collapse of a cavitational bubble, though the

process remains locally adiabatic, inside the cavity,
temperature shoots up to few thousand degrees.

• At such high local temperature, the weak intermolecular

forces (in the form of bonds) are disrupted.

• This thermal dissociation or breakage of molecules

gives oxidative species like OHo, HO2o, Oo and peroxy
compounds H2O2 and O3 inside the cavity.
• The formation of OHo radicals takes place inside the
cavity in the presence of ultrasound by pyrolysis.

• The pyrolysis takes place inside the cavity and near the
interface of the cavity and surrounding liquid at the time
of collapse of the cavity in the presence of ultrasound.

• Pyrolysis takes place because of the very high

temperatures reached during cavitation.
• Phenols, chloro-phenol, nitrophenol, parathion, etc. are among a few
regularly observed contaminants in an industrial effluent, which are
known to get degraded by the cavitation phenomenon.

• Also, ultrasound has been studied for the waste water treatment of
various pollutants such as aromatic compounds, chlorinated
aliphatic compounds, explosives, herbicides and pesticides, organic
dyes, organic and inorganic gaseous pollutants, organic sulfur
compounds, oxygenates and alcohols, pharmaceuticals, personal
care products, pathogens and bacteria in water.

• But due to the inefficient conversion of energy in producing

ultrasonic cavitation and possible difficulties in its scale up, no
industrial installations for waste water treatment have been reported
in the literature.
• Guangming Zhang et al. studied, a new method to
improve the microbial activity of the activated sludge for
wastewater treatment.

• The results showed that the bio-activity of the activated

sludge, expressed as oxygen utilization rate (OUR),
could be enhanced by ultrasonic irradiation.

• The optimal sonication conditions were sound frequency

of 25 kHz, power density of 0.2 W/ml and duration of 30
s; under which the sludge OUR increased by 28%, the
bio-mass growth rate increased by 12.5%, and the
wastewater chemical oxygen demand (COD) and total
nitrogen removal efficiency increased by 5–6%.
 Conclusion
• Overall, cavitation can be effectively applied for a variety
of physical/chemical transformations, including chemical
synthesis, biotechnology, environmental engineering,
polymer engineering, nanotechnology, crystallization,
emulsification, extraction etc. Also, the rates of
transformation are at times, order of magnitude higher
compared to the conventional approach, and energy
consumption is relatively less.

• More insight into intensification studies using process

intensifying parameters and/or a combination of different
reactor configurations/processes should help in
achieving the goal of industrial-scale application.

• Definitely, combined efforts of chemists, physicists,

chemical engineers and equipment manufacturers, will
be required for the Chemical Process Industry to
harness cavitation as a viable option for process
intensification.
THANK YOU