ULTRASONIC SPECTROSCOPY

A Presentation by-

B.Poojitha,

Aditya Institute Of Pharmaceutical sciences & Research

IInd M.Pharmacy , Pharmaceutical Analysis And Quality Assurance .

What is ULTRASOUND?

IS High Frequency (above the Audible Range) which is taken to be above 20kHz.

What is USS?

USS Stands for ULTRASONIC Spectroscopy , measures the change in a Ultrasound Signal per unit distance as it propagates through a material .The interaction of the Ultrasonic and the material causes a energy loss in the wave which is specific to the material.

What can USS be used for?

USS can be used to characterize the Density and

Viscosity of the Material .With addition Analysis it can

determine Solids loading and Particle size

distribution.

What type of materials can be measured?

USS is currently only used on Liquid and pure liquids

, mixtures of liquids ,emulsions ,slurries and soft

solids.

Why USS?

Non-destructive ,

Applicable to optically opaque materials ,

Fast data acquisition allows real time analysis to

IntroductionUltrasonic or Ultrasound is derived from Latin word

Ultra means Beyond and Sonic means Sound .

Ultrasound is beyond the audible range having a

frequency of more than 20,000cycles per second. Is

simply spectroscopy employing SOUND WAVES

.Particularly uses a High Frequency ACOUSTIC

WAVE .

ACOUSTIC WAVE means the sense of hearing

,designed to respond .Similarly those used by

dolphins for communication and bats for navigation

.Sounds in the range 20-100kHz are commonly used .

Much higher frequencies, in the range 1-20

MHz, are used for medical ultrasound. Such

sounds are produced by ultrasonic transducers.

These waves probe Intermolecular forces in

materials.

At higher power levels ,ultrasonic's is useful for

changing the chemical properties of substances .

USS refers to a measurement method in which US

sound waves over a range of frequencies are pulsed

through a liquid medium .

USS is sensitive to particles with radius between

about 10nm to 1000um . The maximum particle

concentration which can be analyzed varies

between about 10 and 50wt% depending on the

nature of the system .

PURPOSE: Is to determine the frequency

dependent properties of materials like attenuation

, velocity .

Sound waves travel Slowest through Gases , Faster

through Liquids and Fastest through Solids .

Principle & Working

PRINCIPLES.

Based on the measurements of two independent parameters-

a)Ultrasonic Attenuation and

b)Ultrasonic Velocity

a)Ultrasonic Attenuation: Is determined by the ENERGY LOSSES in Ultrasonic waves , which includes Absorption and Scattering contribution.

•Expressed in the terms of Viscosity of the Medium….

• Allows Analysis of Kinetics of Fast Chemical Reactions ,Microstructure of Materials including Particle sizing , Aggregation , Gelation , Crystallization and other processes and Characteristics.

•Ultrasonic Attenuation measurement in

Heterogeneous systems ,like Emulsions or colloids

yields information on Particle size distribution.

•Can be used for Extensional rheology

measurement.

•As measurement of Attenuation do not require

High Temperature Stability of the Sample ,they can

be performed in the Large Samples.

b) Ultrasonic Velocity: Is determined by the Density

and the Elastic response of the sample. This

parameter is extremely sensitive to the molecular

organization and intermolecular interactions in the

medium and can be used to analyze a broad range

of molecular processes.

The general principle of high-resolution

ultrasonic measurements as shown in

Figure .

1. The generated electronic signal is

transferred by the piezotransducer into

the ultrasonic wave travelling through the

sample.

2. Another piezotransducer then transfers

the received ultrasonic wave into an

electronic signal, which is subsequently

Particle-Ultrasonic Wave

InteractionsThe four important types of interactions between

an Ultrasonic wave and a colloidal dispersion

are:

I. Intrinsic Absorption : Each of the individual

component phases of a colloidal suspension

absorbs Ultrasound as a result of

classical(viscous and thermal) and relaxation

loss mechanisms.

II.Visco-Inertial Dissipation Losses:In the

presence of an ultrasonic wave a particle

oscillates backwards and forwards because it

has a different density to that of the surrounding

liquid.

This oscillation is damped by the surrounding

Amplitude of ultrasonic wave.

III.Thermal Dissipation Losses:Temperature of

particle periodically increases and decreases

relstive that of the surrounding liquid.

The temperature gradient which arises at the

particle surface causes a net flow of heat out of

the deoplet, which leads to a reduction in

Amplitude of ultrasonic wave.

IV. Scattering losses.

The pulsation and oscillation of a

particle in the presence of an

ultrasonic wave causes the generation

of secondary ultrasonic wave by the

particle.

Thus, some of the ultrasonic energy

associated with the incident wave is

re-directed into different directions and

an increase in attenuation coefficient

may be detected.

INSTRUMENTATION PARTS

A typical Ultrasonic spectrometry consists of a

Single Transmitter ,

A Single Analyzer and

A Measurement Cell.

ULTRASONIC INSTRUMENT

In a Resonator device, the sample to be analyzed

is placed in a thermostated measurement cell

between two parallel piezoelectric ultrasonic

transducers: a transmitter and a receiver.

A signal generator produces an electrical

sinusoidal wave of appropriate frequency and

amplitude.

This wave is applied to the transmitter where it is

converted into a sinusoidal ultrasonic wave that

propagates into the sample.

The ultrasonic wave undergoes multiple

reflections between the two transducers which

results in the formation of a stationary wave .

The signal detected by the receiving transducer

is amplified and relayed to a signal analyzer.

The amplitude of the received signal goes

through a series of maxima and minima, due to

constructive and destructive interference, when

the frequency of the ultrasonic wave is varied.

Lead Zirconate Titanate (PZT)

The piezoelectric material which had the widest

application as an ultrasonic transducer for medical

diagnostic applications is lead zirconate

titanate, commonly referred to as PZT, a shortened

form of the chemical symbols PbZrTi.

Crystals which acquire a charge when

compressed, twisted or distorted are said to be

piezoelectric. This provides a convenient transducer

effect between electrical and mechanical

oscillations. Quartz demonstrates this property and

is extremely stable. Quartz crystals are used for

watch crystals and for precise frequency reference

crystals for radio transmitters.

Barium titanate, lead zirconate, and lead titanate

are ceramic materials which exhibit piezoelectricity

and are used in ultrasonic transducers as well as

microphones. If an electrical oscillation is applied to

such ceramic wafers, they will respond with

mechanical vibrations which provide the ultrasonic

sound source.

The standard piezoelectric material for medical

imaging processes has been lead zirconate titanate

(PZT).

Technical parameters of the model

Two 1ml cells for parallel or differential sample analysis

Digitally Controlled Stirring System

Frequency Range from 2 to 18 MHz (cells with extended

frequency range are available on request)

High-Resolution & Reproducibility (down to 0.2mm/s for

Velocity and 0.2% Attenuation)

Variety of Measurement Regimes:

•Temperature Ramp Mode

•Kinetic Mode

•Titration Mode

•Multi-Frequency Mode

Temperature Range -20ºC to 120ºC (standard) and -40ºC to

150ºC (extended)

Absolute Temperature Control down to 0.01ºC

EXTERNAL MODULES A choice of external modules: the standard 1ml

differential cells for liquids, 1 ml flow through cells for

fast continuous measurements of samples in

flow, differential 1.5 ml cells for semi-solids materials

and custom made fill in or follow-through cells 0.03

to 4 ml sample volume range.

The cells can be plugged to HR-US 102-P, HR-US

102 SS-P and HR-US 102 FT-P spectrometers.

External Cell for the Analysis of LIQUIDS

External Cell for Analysis of SEMI-SOLIDS

External FLOW THROUGH Cell for

measurements in FLOW

Versatile high resolution ultrasonic

spectrometer for analysis of

liquids The HR-US 102 high-resolution ultrasonic spectrometer

provides a broad range of analytical capabilities for

liquids. The spectrometer is equipped with precision

temperature controller and digital stirring system and can

perform measurements in dilute and concentrated

solutions, suspensions and emulsions in various

regimes: kinetics, temperature ramp, titrations and

others. The spectrometer is equipped with two 1ml

cells, which can be used independently or in differential

measurements.

Also available as P-model which offers extended

capabilities by allowing the user to attach external

modules.

Versatile high resolution ultrasonic

spectrometer for analysis of

liquids with extended capabilitiesThe HR-US 102 P high-resolution ultrasonic

spectrometer has the same configuration as the HR-

US 102 with additional interface, which offers

extended capabilities by allowing user to attach

external modules such as cells for semi-solid

materials, measurements in flow, etc.

HR-US 102 P

Ultrasonic Colloid Stability

AnalyzerThe NEW HR-US Colloid Stability Analyzer is

designed to enable the analysis of stability, shelf-life

and effects of thermal treatment of

emulsions, suspensions and other complex

formulations in R&D, product development, and

QA/QC environments of various industries, including

pharmaceutical, food and beverage, cosmetics and

personal care.

High throughput ultrasonic

spectrometer for analysis of

liquids The HR-US 102 HTP high throughput ultrasonic

spectrometer equipped with semi-automated sample

introduction system, which allows fast

filling, emptying and cleaning of the ultrasonic cells.

Can do the measurements in continuous flow. Ideal

for routine repeatable measurements in analytical

labs.

Also available as P-model which offers extended

capabilities by allowing the user to attach external

modules.

HR-US 102 HTP

Titration Kinetic Analyzer (TKA)The Titration Kinetic Analyzer measures micro

structural and molecular processes in liquids when

concentration of selected compounds is changed

(titration), or with time, when a chemical reaction is

started by an injection of a required compound.

This provides a valuable tool for product and

process development .

TKA requires only 0.04 ml of sample allows cost-

effective analysis of expensive materials such as

proteins, nucleic acids and antibodies. The Titration

Kinetic Analyzer does not require any optical activity

of analyzed compounds and can analyze molecular

binding and chemical reactions in optically non-

transparent samples such as blood. In addition, the

Analyzer has the unique ability to follow

simultaneously an analyzed molecular process .

Examples of application of TKA include

measurement of binding constants, drug

screening, enzymatic activity, kinetics of chemical

reactions and others. The device is based on the

patented principles of High-Resolution Ultrasonic

Spectroscopy and consists of sampling and

measuring modules. It is PC controlled, robotic

compatible, has flexible , the determination of grain

size in metals and quality control in carbon-fibre

composites and glued joints .

BENEFITSMost materials are ultrasonically transparent

allowing the analysis of a broad variety of sample

types, chemical reactions and processes.

Hence, Ultrasonic analysis can now be easily

performed in

chemistry, physics, biotechnology, pharmaceuticals,

agriculture, environmental control, medicine

Modern ultrasonic cells do not have sharp corners

and can accommodate even aggressive liquids

such as strong acids or organic solvents without

evaporation in

the course of measurements sizes range from 4ml

down to 30µl.

The measurements are completely computer

controlled and results are presented in a

graphical,digital format, which is compatible with

USES•Determination of molecular compressibility ,

•Determination of reaction rates,

•Changes in tertiary of large molecules like Proteins

,

•Aggregation

•On line monitoring for process control.

•Used in the analysis of sedimentation and

aggregation of drugs prepared using different

polymer coatings.

•Used in measurement of concentration profile and

sedimentation for suspensions in flow .

ADVANTAGES

Ultrasonic Spectroscopy has many advantages

over other existing particle sizing technology

because it is

• Non-destructive in nature

•Non-invasive in nature

• Used to characterize systems which are

concentrated and optically opaque

•Capable of rapid measurement

DISAVDANTAGE

Is not suitable for dilute suspensions that is with

concentrations less than 1%wt.

APPLICATIONS

a)To evaluate stability of EMULSIONS:Is a key

element for evaluation of the life-time and

Temperature conditions for storage and use of

emulsion based products .Ultrasonic's

measurements allow very simple procedures for

evaluation of the stability of Emulsion.

b)To determine particle size distribution of colloidal

systems

c)In the analysis of Micro emulsions

•In addition, the ultrasonic velocity and attenuation

can be measured simultaneously at different

wavelengths as a function of the time for analysis

of kinetics of chemical reactions and processes.

•Analysis of enzymatic activity is an application of

this technique.

REFERENCES

http://www.signal.uu.se/Publications/pdf/l061.pd

f

http://jbsr.pharmainfo.in/documents/vol3issue3/2

011030302.pdf

http://www.kenelec.com.au/sitebuilder/products/

files/902/processultrasoundspectroscopyforin-

situcharacterisation1.pdf

Simultaneously measuring concentrations of a

model drug and a model excipient in solution

using ultrasonic spectroscopy

Raymond R>Chen ,Todd Zelesky , Nicholoas

Ilasi , Sonja S. Sekulic

Ultrasonic attenuation spectroscopy of

emulsions with droplet sizes greater than 10um

Andreas Richter , Tino Voigt , Sigefried

Ripperger

Dependence of Ultrasonic attenuation on the

material properties

Frank Babick , Frank Hinze , Sigefried Ripperger

Ultrasonic attenuation spectroscopy study of

flocculation in protein stabilized protein

Kyros Demetriades ,D.Julian McClements

Ultrasonic spectroscopy and X-ray Diffraction

study of ARB aluminum

K . Hirai , T. Ichitsubo , E.Matsubara and N.Tsuji

High Resolution Ultrasonic spectroscopy for

Liquid chromatography

Ultrasonic spectroscopy : A promising tool for

material Analysis

M.S. kondawar and L.S. Untwal

Ultrasonic spectroscopy and Differential

Scanning Calorimetry of Liposomal

Encapsulated Nisin

T.Matthew Taylor , P.Michael Davidson , Barry

D>Bruce , and Jochen Weiss

http://books.google.co.in/books?id=NzF_KrMZ4

7IC&pg=PA38&lpg=PA38&dq=why+ultrasonic+s

pectroscopy+non+destructive%3F&source=bl&ot

s=dxaiP6XOnn&sig=n7rwlSvU3l5Bu7s_w8gnYX

2b7cY&hl=en&sa=X&ei=r1xcU5a7CJHMrQfgx4A

I&redir_esc=y#v=onepage&q=why%20ultrasonic

%20spectroscopy%20non%20destructive%3F&f