Pharmaceutical imaging techniques (2)

PHARMACEUTICAL
IMAGING TECHNIQUES

PRESENTED TO: PRESENTED BY:
Mrs.Shilpi Agarwal Sakshi Taneja
M.Pharm 1st year
ISF College Of Pharmacy
MOGA,PUNJAB

Definition
 The visual representation of an object, such as a body
part or pharmaceutical product, for the purpose of
checking pharmaceutical process or data collection or
disease diagnosis , using any of a variety of usually
computerized techniques, such as ultrasonography or
spectroscopy.

 Imaging technologies are receiving much attention in
the pharmaceutical industry because of their potential
for accelerating drug discovery and development.

http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-
discovery-and-development.html

http://www.answers.com/topic/imaging#ixzz1axlAHIgt

History
 1895 – Roentgen discoverd x-rays

 1896 - Edison created fluoroscope

 1896 - Bequerel discovered radioactivity

 1957 – Ian Donald discovered ultrasound

 1958 – Hal Anger – Gamma Camera

 1973 – Hounsfield invented CT scanner

 1984 – Damadian – FDA approved MRI

 2000 – Time – CT/PET - invention of the year

http://www.authorstream.com/Presentation/Laurie-54439-Basics-Molecular-Imaging-
ImagingThe-Future-Radiology-Topics-Definitions-of-molec-Education-ppt-powerpoint/

Types
Chemical Imaging

Biophotonic Imaging

Elemental Imaging

Molecular Imaging

Digital Imaging

Chemical Imaging for
Pharmaceutical Testing
 Chemical imaging is a non-destructive
imaging technique that combines spatial
and spectral information to provide a
more complete characterization of a
sample

http://www.gatewayanalytical.com/industris-served/pharmaceutical/industry-
leaeding-chemical-imaging-experts

History
 Commercially availablelaboratory-based
chemical imaging systems emerged in the
early 1990s.

 Initially used
for novel research in
specialized laboratories, chemical imaging
became analytical technique used for
general R&D, quality assurance (QA) and
quality control (QC) in less than a decade.
http://en.wikipedia.org/wiki/Chemical_imaging

Principle
 Chemical imaging shares the
fundamentals of vibrational spectroscopic
techniques.
 Vibrational spectroscopy measures the
interaction of light with matter. Photons
that interact with sample absorbed, and
the pattern of absorption provides
information, or a fingerprint, on the
molecules that are present in the sample.

Applications
 Content and Blend Uniformity in granulation
mass during tablet manufacture.

 Characterization and Identification of
Polymorphs during preformulation process.

 In Vitro Particle Characterization.
 Ingredient-Specific Particle Size distribution
 Ingredient-Specific Particle Shape
 Particle Interaction
 Aggregation and Agglomeration Studies


Elemental Imaging
 The analysis of the distribution of
pharmaceutical materials in tablet
formulations, such as drugs and matrix
elements, is critical to product performance
and is used in such areas as quality control,
impurity testing, and process monitoring.

 Micro X-ray Fluorescence (MXRF)
elemental imaging offers complementary
information to molecular imaging techniques

http://www.icdd.com/resources/axa/vol48/V48_37.pdf

Applications
MXRF was is for the elemental imaging
of various commercial pharmaceutical
drug and vitamin supplements.

Specifically, elementalcomposition and
heterogeneity are monitored for each
different tablet.


Digital Imaging
 Digital imaging or digital
image acquisition is the
creation of digital images,
typically from a physical
scene.
 The term is often assumed to
include the processing,
compression, storage,
printing, and display of such
images. The most usual
method is by digital
photography with a digital
camera.

http://en.wikipedia.org/wiki/Digital_imaging

History
 Digital imaging was
developed in the 1960s and
1970s, largely to avoid the
operational weaknesses of
film cameras, for scientific
and military missions
including the KH-11
program.

 As digital technology
became cheaper in later Camera imaging system for leak
decades it replaced the old detection in blister packs
film methods for many
purposes.


Applications
 Capturing Images of Culture Plates.
 To record positive QC results, many microbiology
departments use either a standard or digital camera.
 Findings have to be recorded so that recommendations
can be backed up and decisions on the appropriate
course of action are available for discussion between
production managers and QC department personnel.
 Protecting pharmaceutical products against
counterfeiting or identifying fraudulent import of
donated or discounted drugs.


Contd.
 Quantification
andCharacterization of Visible
and Sub-Visible
Pharmaceutical Particles.

 The FlowCAM Series of
imaging particle analyzers
combine industry-leading
image quality with automated
statistical pattern recognition
software to produce the most
powerful sub-visible particle FlowCAM
analyzer available for the
pharmaceutical industry.

http://www.fluidimaging.com/Collateral/Documents/English-
US/Literature/Pharma_FlowCAM_Flyer_200ppi.pdf

Contd.
 Characterization of
particle sizes in bulk
pharmaceutical solids
using digital image
information.

 Digital surface images
of various granule
batches are captured
using an inventive
optical setup in
controlled illumination CAMSIZER- Digital Imaging -
conditions. Particle Size/Shape Analyzer

http://www.fluidimaging.com/Collateral/Documents/English-
US/Literature/Pharma_FlowCAM_Flyer_200ppi.pdf

Imaging Techniques
 Terahertz Pulsed Spectroscopy

 In-Vitro Tomography

 Magnetic Resonance Imaging

 Near Infra-Red Spectral Imaging

 Raman Spectroscopy

Contd.
 Fluorescence correlation spectroscopy

 Micro-xray Fluorescence

 Hyperspectral Imaging

 Optical Coherence Tomography

Fluorescence Correlation
Spectroscopy
 Among the large number of optical methods that
have been developed for biological and
chemical investigations, FCS plays the largest
role today, especially in the field of single-
molecule analysis.

 Itbears not only a high intrinsic optical
efficiency, but also provides information about
the molecular environment and structure in
many different ways
http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html

History
 The history of the FCS is relatively long more
than 30 years.

 The idea of the FCS was proven in the beginning
of 1970s by Cornell Univ.

 The recent boom of the FCS research beginning
from the early 1990s had to wait the development
of the electronics, computer, optics, and lasers.

 The first commercial instrument was released by
Zeiss in 1996.


Principle
 FCS system uses a confocal microscope .

 He-Ne lasers, can be an excitation source of the
fluorescence microscope.

 A pulse compensator may be used to optimize the
excitation efficiency.

 A high numerical aperture objective lens focuses
the excitation beam into the diffraction limited
spot, and effectively collects the fluorescence
from the sample.


Contd.
 A dicroic mirror separates the fluorescence from the
excitation beam and a long pass filter or an
interference filter passes appropriate wavelength of
fluorescence.

 The fluorescence spot is imaged on a small pinhole
aperture.

 The fluorescence through the pinhole is focused again
on a detector.

 An avalanche photo diode (APD) detector is used as
the photon counting detector.

Applications
 It is based on a computer-aided
spectrofluorimeter.

 When applied to pharmaceutical
dosage forms, Eg. it gives good
selectivity for a particular drug.

 Good calibration linearity,
precision and recovery are
observed for both principal drug
components.

 This novel technique can provide
an improved method for
generating diagnostic profiles of
drugs, degradation products and
metabolites.
http://www.sciencedirect.com/science/article/pii/S0003267000817249

Contd.
 Fluorescence detection and characterization has found a
wide use within biomedical research.

 For drug development activities in biotechnological and
pharmaceutical industries.

 It is particularly heavily used in the pharmaceutical
industry where it has almost completely replaced
radiochemical labelling.

http://www.sciencedirect.com/science/article/pii/S0003267000817249

Micro X-ray Fluorescence (MXRF)
 Micro-x-ray fluorescence(MXRF) is
among the newest technology used to
detect fingerprints.

 It is a new visualization technique which
rapidly reveals the elemental composition
of a sample by irradiating it with a thin
beam of X-rays without disturbing the
sample.
http://en.wikipedia.org/wiki/Micro-X-ray_fluorescence

History
 It was discovered recently by scientists at the Los
Alamos National Laboratory.

 The newly discovered technique was then first
revealed at the 229th national meeting of the
American Chemical Society, the world’s largest
scientific society.

 This new discovery could prove to be very
beneficial to the law enforcement world, because
it is expected that MXRF will be able to detect the
most complex molecules in fingerprints.

http://en.wikipedia.org/wiki/Micro-X-ray_fluorescence

Principle
 When materials are exposed to short-
wavelength X-rays , ionization of their
component atoms takes place.

 Ionization consists of the ejection of
electrons from the atom.

 This expels tightly held electrons from the
inner orbitals of the atom.

 The removal of an electron renders atom
unstable, and electrons in higher orbitals
"fall" into the lower orbital .

 In falling, energy is released in the form of
a photon,which is detected then.

http://en.wikipedia.org/wiki/X-ray_fluorescence

Applications
 They are able to analyze
coating thicknesses and
changes in composition
as a function of coating
depth.

 Micro XRF is a non-
destructive testing
technique providing
elemental analysis suited
to applications including,
forensics, art, failure
analysis,
microelectronics etc.

http://en.wikipedia.org/wiki/X-ray_fluorescence

Contd.
 3D micro-X-ray fluorescence analysis (3D
XRF) is used for the non-destructive study of
pharmaceutical tablets.

 Measures the distribution of several inorganic
elements (Zn, Fe, Ti, Mn, Cu) from the surface
to a depth of several hundred microns under the
surface.
http://www.mendeley.com/research/sodium-polyacrylate-as-a-binding-agent-in-
diffusive-gradients-in-thinfilms-technique-for-the-measurement-of-cu2-and-
cd2-in-waters/

Contd.
 MXRF can detect elemental composition for a
given sample by measuring its characteristic x-ray
emission wavelengths or energies.
 Mesoscale ( > 10 µm2) analysis is achieved
through the use of a polycapillary focusing optic
in conjunction with a Rh x-ray tube source.
 MXRF allows for simultaneous elemental analysis
with both quantitative and qualitative analysis
of elements.
 It is a nondestructive technique and requires
minimal sample preparation.
http://www.dxcicdd.com/04/PDF/T_Miller_1.pdf

Hyperspectral imaging
 Since the year 2000
hyperspectral imaging
systems have been
commercially available for
macroscopic and
microscopic chemical
analysis.

 Such a technique is highly
relevant for pharmaceutical
industry. Indeed, the
homogeneity of the
different components of a
tablet is an essential factor
for its quality.
Hyperspectral Camera

http://www.image-and-vision.com/Christelle_recherche_en.html

Principle
 The hyperspectral camera
collects both spatial and spectral
information.

 Camera images one line of the
product at a time and as the
sample tray or product moves
underneath the camera , the
whole image is collected.

 A full spectrum of each point is Spectral signatures of generic tablets
saved, resulting in a "hypercube"
of data that can be analyzed to
identify chemically distinct
components and their spatial
distribution within the product.

http://www.middletonresearch.com/applications/hyperspectral-imaging-
pharmaceutical.php

Applications
 Hyperspectral imaging, or chemical
imaging, is ideal for analyzing solid
form pharmaceutical products such as
films, blends, and tablets either during
on-line manufacturing or in laboratory
formulation development.

 By collecting spatial and spectral
(chemical) information simultaneously,
one can rapidly image a sample or
product line.
Hyperspectral Imager targets process
manufacturing
 Hyperspectral imaging provides
information about the spatial
distribution of chemical components
within the sample.
http://www.middletonresearch.com/applications/hyperspectral-imaging-pharmaceutical.php

Contd.
 The homogeneity or
patterned dispersion of
chemical components
is known.

 Number of tablets that
a typical near- IR
camera can currently
analyze simultaneously
was estimated to be Hyperspectral Imager
approximately 1300.

http://spiedigitallibrary.org/proceedings/resource/2/psisdg/4626/1/136_1?isAuthorize
d=no

Other applications
 Particle morphology and size distribution can be characterized by
techniques such as scanning electron microscopy (SEM) and X-ray
diffraction (XRD) .

 Atomic force microscopy (AFM) has been used to study the effects
of mechanical processing on surface stability of pharmaceutical
powders .

 Total reflection X-ray fluorescence (TXRF) has been used to study
trace elements

 Fourier transform near infrared (FT-NIR) methods have been used
to study the distribution of different organic ingredients in tablets
with a spatial resolution of ~20-100 μm .


Terahertz pulsed spectroscopy
 Terahertz pulsed
spectroscopy (TPS)
and terahertz pulsed
imaging (TPI) are
two novel techniques.

 Used for the physical
characterization of
pharmaceutical drug
materials and final
solid dosage forms.

http://ieeexplore.ieee.org/Xplore/login.jsp?url=http%3A%2F%2Fieeexplore.ieee.org%2Fiel5%2
F19%2F4014679%2F04014688.pdf%3Farnumber%3D4014688&authDecision=-203

Applications
 To characterize crystalline properties of
drugs and excipients.
 Different polymorphic forms of a drug can
be readily distinguished and quantified.
 measurement of coating thickness .
 uniformity in coated pharmaceutical tablets
 structural imaging and 3D chemical imaging
of solid dosage.
http://ieeexplore.ieee.org/Xplore/login.jsp?url=http%3A%2F%2Fieeexplore.ieee.org
%2Fiel5%2F19%2F4014679%2F04014688.pdf%3Farnumber%3D4014688&authDec
ision=-203

In-vitro tomography
 Tomography is the
method of imaging a
single plane, or slice,
of an object resulting
in a tomogram.
 It is a non-
destructive imaging
at depth of
pharmaceutical solid
dosage forms.
http://www.ncbi.nlm.nih.gov/pubmed/18778770

History

 It is only over the last fifteen years that
tomography has been applied for the in-
vitro characterisation of dosage forms.

 Tomographic imaging techniques offer
new prospects for a better understanding
of the quality, performance and release
mechanisms of pharmaceutical solid
dosage forms.

Principle
 It consist of passing X-rays and
obtaining information with a
detector on the other side.

 The X-raysource and the detector
are interconnected and rotated
around the material to be imaged.

 Digital computers then assemble
the data that is obtained and
integrate it to provide a cross
sectional image (tomogram) that
is displayed on a computer
screen.

 The image can be photographed
or stored for later retrieval and
use.

http://www.medindia.net/patients/patientinfo/CT_Scan_working.htm

Types
There are several forms of tomography:-
1.Linear tomography: This is the most basic form
of tomography.

2.Poly tomography: This was a complex form of
tomography. With this technique, a number of
geometrical movements were programmed.

3.Zonography: This is a variant of linear
tomography, where a limited arc of movement is
used. It is still used in some centres for visualising
the kidney during an intravenous urogram (IVU).

Industrial applications
 Fault detection and failure analysis

 Assembly inspection of complex mechanisms

 Dimensional measurement of internal components

 Advanced material research

 Research - Material Structure, New Material Analysis, Density of
Analysis

 Inspections like Cracks, Porosities, Displacement, Quality Control


Magnetic resonance imaging

 Magnetic Resonance
(MR) imaging is one
of the principal
modalities imaging
of the samples at
high resolution which
is based on principle of
NMR


Principle
 MRI uses magnets to polarise
and excite hydrogen in water
molecules .

 The MRI machine emits an
RF pulse that specifically
binds only to hydrogen.

 The system sends the pulse to
the area to be cheked.

 Produces a detectable signal
which is encoded, resulting in
images .

http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-discovery-
and-development.html

contd.
The pulse makes the protons
in that area absorb the energy
needed to make them spin in a
different direction.

 The particular frequency of
resonance is called the
Larmour frequency.


Instrumentation
 The principal components are the magnet,
radiofrequency (rf) coils and the gradient coils.

 The majority of MR systems use super
conducting magnets.

 Most currently produced magnets are based on
niobium-titanium (NbTi) alloys.

 The rf coils used to excite the nuclei usually are
quadrature coils which surround the head or
body.
http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-discovery-
and-development.html

Applications
 image analysis for
assessment of HPMC
matrix tablets
structural evolution in
USP Apparatus 4.

 MRI provides a means
Distribution of Mn2+ in the eye after 20
to non-invasively and min of 3 mA transscleral iontophoresis
continuously monitor applied on the sclera next to the limbus
ocular drug-delivery
systems with a contrast
agent .
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728085/figure/F3/

Contd.
Amphiphilic
hyperbranched
fluoropolymers as
nanoscopic 19F
magnetic resonance
imaging agent
assemblies.

It is a useful technique in

 pharmacokinetic studies,
 evaluation of drug-delivery methods
drug-delivery device testing

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744969/figure/F3/

Optical coherence tomography
 The enormous commercial potential of OCT is evidenced by a
September 2010 report from the Millennium Research Group
(Toronto, ON, Canada).

 Optical coherence tomography (OCT) is a recently developed
optical technique that produces depth profiles of three-dimensional
objects.

 It is a nondestructive interferometric method responding to
refractive index variation in the sample under study and can reach a
penetration depth of a few millimetres.

 OCT employs near-infrared (NIR) light and therefore provides a
link between NIR spectroscopy and Terahertz (THz) measurements

http://en.wikipedia.org/wiki/Optical_coherence_tomography

Schematic diagram

http://www.laserfocusworld.com/articles/print/volume-47/issue-8/features/optical-
coherence-tomography-oct-supports-industrial-nondestructive-depth-analysis.html

Applications
 The analysis of
pharmaceutical tablets and
coatings.

 It is also an attractive
candidate technology for in-
line quality control during
manufacturing.

 It allows rapid evaluation of
coating properties, such as
thickness and homogeneity
independently from variations
of the tablet core.

http://iopscience.iop.org/0034-4885/66/2/204

Near-infrared spectral imaging
 Near-infrared
spectroscopy (NIRS)
is a spectroscopic
method that uses the
near-infrared region of
the electromagnetic
spectrum (from about
800 nm to 2500 nm).

 Itsspectral range is
0.7-5 microns and
temperature is 740-
3000 degree kelvin. Near infrared imaging system: the
Sapphire from Malvern company
http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf

Principle
 NIR detects the presence of
different chemical bonds,
particularly O-H, N-H and C-
H, by measuring optical
absorption.

 Quartz halogen lamps provide
source of illumination.

 Images are captured using a
two-dimensional array.
Used in process quality control
 The array, eliminates the need
to move the sample relative to
the detector.


Applications
 In quality assurance of
pharmaceutical products:
analysis of tablets to assess
powder blend homogeneity.

 Modern NIR systems can be
configured to study either a
small sample - a single
granule,or a larger region,
perhaps a complete blister
pack.

 This flexibility makes NIR THE FOSS XDS based on NIR is
suitable for high throughput MultiVial Analyzer
QA/QC applications as well
as in depth laboratory analysis


Contd.
 Assessing the impact of processing conditions on moisture
content- Hydroxyl groups are strong NIR absorbers, can be
used to detect water in a sample.

 Investigating the nature of material in a sample -With NIR
it is even possible to distinguish water that is bound to other
sample components (forming hydrates) from water simply
present within the sample (bulk water).

 Investigating the homogeneity/heterogeneity of Granule:
Coated granules are often designed to have a homogeneous
core surrounded by a uniform coating.In practice, however,
an active pharmaceutical ingredient (API) may be distributed
unevenly.


Contd.
 With NIR, granules can be investigated individually or
as a complete dose. Imaging individual granules is
beneficial particularly for coated materials.

 Coating uniformity can therefore be quantitatively
assessed.

 API surface coverage can be measured directly by
appropriately processing spectral data.

 Because the technique is non-destructive, the same
samples that have been analyzed using NIR-CI may
subsequently be subjected to dissolution testing.

Raman Spectroscopy
 Raman
spectroscopy named
after C. V. Raman.

 Used to study
vibrational,
rotational, and other
low-frequency modes
in a system.

http://en.wikipedia.org/wiki/Raman_spectroscopy

Principle
 It relies on inelastic scattering, or
Raman scattering, of
monochromatic light, usually
from a laser in the visible, near
infrared, or near ultraviolet range.

 The laser light interacts with
molecular vibrations, photons or
other excitations in the system,
resulting in the energy of the
laser photons being shifted up or
down.

 The shift in energy gives
information about the vibrational
modes in the system

http://en.wikipedia.org/wiki/Raman_spectroscopy

Applications
 Polymorph control

 Content uniformity

 Blend uniformity

 Rapid composition analysis

 Exotic formulations

 And much more... including:
◦ Contamination ID
◦ Particle Size
◦ HTS and Transmission Raman
◦ PAT/Process kinetics
◦ Patent Protection

http://www.renishaw.com/en/raman-spectroscopy-applications--6259

Contd.
 Polymorphism:ideal tool for the characterization of different
polymorphic forms of active pharmaceutical ingredients (API) and
excipients. The ARAMIS and XploRA series are ideal for
polymorphic analysis.

 Blend Uniformity:Whether it is lab, scale-up or manufacturing,
Raman probes enables monitoring of blending uniformity and end
point detection.

 Exotic Formulations:The high spectral and spatial resolution of
confocal Raman microscopes is critical in characterizing innovative
drug delivery systems such as stents, micro-needle patches, nano-
carriers and others.

http://www.renishaw.com/en/raman-spectroscopy-applications--6259

Contd.
Particle Size Analysis:
Sizes of particle is critical in determining bio-availability. Raman
microscopes can determine particle and agglomerate sizes in the
finished product.

Contamination:
The Raman and XRF microscope can detect trace
contamination, whether it is a foreign material or
product degradation, helping root cause analysis issues
within manufacturing processes and quality control.

Confocal laser scanning
microscopy (CLSM)
 Means Light Amplification by
Stimulated Emission of Radiation.

 Phenomenon is brought about
using devices that transform light
of varying frequencies into a single
intense, nearly nondivergent beam
of monochromatic radiation in the
visible region.
The LSM 700 Laser Scanning
 Lasers operate in the visible, Microscope from Carl Zeiss
infrared, or ultraviolet regions of
the spectrum.

 They are capable of producing
immense heat and power when
focused.

http://www.xenogen.com/glossary.html

History
 Confocal microscopy was originally patented by Marvin Minsky in
1957.

 In 1978, Thomas and Christoph Cremer designed a laser scanning
process, which scans the three dimensional surface of an object.

 This CLSM design combined the laser scanning method with the 3D
detection of biological objects labeled with fluorescent markers for the
first time.

 During the next decade, confocal fluorescence microscopy was
developed into a fully mature technology, in particular by groups
working at the University of Amsterdam and the European Molecular
Biology Laboratory (EMBL) in Heidelberg.

http://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy

Principle
 In a confocal laser scanning
microscope, a laser beam passes
through a light source aperture.
 Then it is focused by an objective
lens on the surface of a specimen.
 Scattered and reflected laser light
from the illuminated spot is then
re-collected by the objective lens.
 A beam splitter separates off some
portion of the light into the
detection apparatus.
 After passing a pinhole, the light
intensity is detected by a
photodetection device,
transforming the light signal into
an electrical one that is recorded
by a computer.

Schematic diagram


Applications
 The application of confocal
laser scanning microscopy is
in the physicochemical
characterisation of
pharmaceutical system.

 It is being exploited to study a
wide range of pharmaceutical
systems, including phase-
separated polymers, colloidal
systems, microspheres, pellets,
Confocal Laser Scanning
tablets, film coatings, Microscope for 300mm Wafer
hydrophilic matrices, and Observation/OLS3000-300
chromatographic stationary
phases


Contd.
 Using CLSM the importance of setting up the
appropriate distance between the coating nozzle
and the powder bed with respect to
microparticle coating quality in fluidized bed
processing is known.

1. Coating quality was found to decrease with increasing distance
the coating droplets have to travel before impinging onto the core
particles as a result of spray-drying of the coating droplets.
2. Also, coating quality decreased with increasing viscosity of the
coating droplets, resulting in reduced spreading on the cores.


Contd.
 In the examination of the embedment and
the release characteristics of chemical
permeation enhancers from transdermal
drug delivery systems (TDDSs) of the
"drug-in-adhesive" type.

 CLSM is demonstrated to be an excellent
tool to study how enhancers are
incorporated and diffuse into a TDDS.

Photo Multiplier Tube (PMT)
 A vacuum phototube with additional
amplification by electron
multiplication .

 It consists of a photocathode, a series
of dynodes, called a dynode chain on
which a secondary- electron
multiplication process occurs, and an
anode.

 Different types of dynode structures
have been developed, e.g. circular
cage structure, linear focused
structure, venetian blind structure,
box and grid structure

http://www.iupac.org/reports/V/spectro/p
artXI.pdf

History
 The photoelectric effect was carried
out in 1887 by Heinrich Hertz who
demonstrated it using ultraviolet
light.

 Elster and Geitel two years later
demonstrated the same effect using
visible light striking alkali metals.

 Historically, the photoelectric effect
is associated with Albert Einstein,
who relied upon the phenomenon to
establish the fundamental principle
of quantum mechanics, in 1905 for
which Einstein received the 1921
Nobel Prize.

http://en.wikipedia.org/wiki/Photomultiplier

Photo
Principle Multiplier
tube

 Photomultipliers are constructed from a glass envelope that
houses a photocathode, several dynodes, and an anode.
 Incident photons strike the photocathode material.
 Electrons being produced as a consequence of the
photoelectric effect.
 These electrons are directed by the focusing electrode toward
the electron multiplier, where electrons are multiplied by the
process of secondary emission.
 The electron multiplier consists of a number of electrodes
called dynodes. Each dynode is held at a more positive
voltage than the previous one.


Contd.
 Upon striking the first dynode, more low energy electrons are
emitted, and these electrons in turn are accelerated toward the
second dynode.
 The geometry of the dynode chain is such that a cascade
occurs with an ever-increasing number of electrons being
produced at each stage.
 Finally, the electrons reach the anode, where the accumulation
of charge results in a sharp current pulse indicating the arrival
of a photon at the photocathode


Applications
 Mass Spectrometers
Analysis of gas molecules by ionising
the molecules,these ions are measured
by targeting them onto a dynode which
produces a shower of electrons onto a
phosphor screen viewed by a
photomultiplier.

 Particle Counting
Many pharmaceutical and electronics
industrial processes have to be carried
out in dust free conditions, a particle
counter is essential to monitor the
amount of airborne particles. Light is
scattered by the particles in a sample
and detected by a photomultiplier, the High-voltage Cascade Multiplier,
amount of light scattered is Electrostatic Gun and its accessories
proportional to the dust concentration.

http://www.et-enterprises.com/photomultipliers/photomultiplier-applications

Contd.
 Liquid Scintillation Counting
(LSC)
Liquid scintillation counting is
widely used for the study of
biological functions, tumours,
viruses, and new drugs. More
famously it is used for
radioactive dating .

 Particle Sizing
The size of particles in powders,
sprays, and emulsions is
important if they are to be
manufactured with the required
properties. Scattered laser light
is detected by a photomultiplier
.

Contd.
 Luminometers
Its application in the food and
pharmaceutical industries is growing.
Example- inspecting products such as meat
and cheese for the presence of antibiotics,
drugs, insecticides.

 Radiation Monitoring
Many people work in the nuclear
pharmaceutical industry where they are
exposed to radiation on a daily basis.
Portable radiation meters incorporating a
photomultiplier and scintillator measure the
radioactive dose received by these workers
or detect radioactive contamination on their
gloves or clothes protecting them from
exceeding a safe level.


Contd.
 Sorting
Transmitted or reflected light measured
by photomultipliers is the basis of many
sorting and inspection techniques used in
manufacturing capsules.

 Chromatography
Photomultipliers are used in instruments
which analyse chemical mixtures by
separating the constituents in a column.


Contd.
 Spectrometry - fluorescence
This technique is widely used for chemical
analysis. A particular wavelength of light
from a Xenon lamp illuminates a
molecular sample causing electrons to be
excited . These subsequently emit light
which is detected by a photomultiplier.

 X-ray Diffractometer Photomultiplier tube (PMT) and
microprocessor control
X-ray crystallography is the study of solid
structures by the diffraction of an intense
beam of x-rays. The angular pattern of x-
rays produced is recorded by a radiation
detector, often a photomultiplier and
scintillator assembly.

TANDEM On-line Tablet
Characterization PAT Tool
 TANDEM is an integrated, automated, on-line
pharmaceutical tablet characterization tool
providing tablet weight, thickness, hardness
and NIR content uniformity analysis.

 Provides tablet weight, thickness, hardness
and NIR content uniformity analysis.

 Measures over 300 tablets per batch instead
of 10 by HPLC.

 Full validation with IQ/OQ/PQ
documentation and USP/EP protocols.

 Can be connected to any tablet press

http://www.brukeroptics.com/tandem.html

Application
 TANDEM provides a comprehensive
solutions for the pharmaceutical industry.

 It provides a full set of tablet
characterization parameters including
weight, size, thickness, hardness, diameter
and NIR content uniformity in a single
analyzer.

 The system consists of a Bruker
MATRIX™ near infrared spectrometer, a
Dr. Schleuniger 10X-T tablet testing Bruker MATRIX – I FT-
system, and a tablet handling unit. NIR SPECTROMETER

 TANDEM can be integrated with existing
tablet pressing systems for automated
analysis.
http://www.brukeroptics.com/tandem.html

Acknowledgement

I owe my thanks to Mrs.SHILPI AGARWAL for
giving me such a topic and guiding me.

Pharmaceutical imaging techniques (2)

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