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

2. Definition The visual representation of an object, such as a bodypart or pharmaceutical product, for the purpose ofchecking pharmaceutical process or data collection ordisease diagnosis , using any of a variety of usuallycomputerized techniques, such as ultrasonography orspectroscopy.Imaging technologies are receiving much attention inthe pharmaceutical industry because of their potentialfor accelerating drug discovery and development.http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-discovery-and-development.htmlhttp://www.answers.com/topic/imaging#ixzz1axlAHIgt 3. 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 yearhttp://www.authorstream.com/Presentation/Laurie-54439-Basics-Molecular-Imaging-ImagingThe-Future-Radiology-Topics-Definitions-of-molec-Education-ppt-powerpoint/ 4. TypesChemicalImagingBiophotonic ImagingElemental ImagingMolecular ImagingDigital Imaging 5. Chemical Imaging forPharmaceutical Testing Chemical imaging is a non-destructiveimaging technique that combines spatialand spectral information to provide amore complete characterization of asamplehttp://www.gatewayanalytical.com/industris-served/pharmaceutical/industry-leaeding-chemical-imaging-experts 6. 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 7. Principle Chemical imaging shares thefundamentals of vibrational spectroscopictechniques. Vibrational spectroscopy measures theinteraction of light with matter. Photonsthat interact with sample absorbed, andthe pattern of absorption providesinformation, or a fingerprint, on themolecules that are present in the sample.http://en.wikipedia.org/wiki/Chemical_imaging 8. Applications Content and Blend Uniformity in granulationmass during tablet manufacture. Characterization and Identification ofPolymorphs during preformulation process. In VitroParticle Characterization. Ingredient-Specific Particle Size distribution Ingredient-Specific Particle Shape Particle Interaction Aggregation and Agglomeration Studies http://en.wikipedia.org/wiki/Chemical_imaging 9. Elemental ImagingThe analysis of the distribution ofpharmaceutical materials in tabletformulations, such as drugs and matrixelements, is critical to product performanceand is used in such areas as quality control,impurity testing, and process monitoring. Micro X-ray Fluorescence (MXRF)elemental imaging offers complementaryinformation to molecular imaging techniques http://www.icdd.com/resources/axa/vol48/V48_37.pdf 10. ApplicationsMXRFwas is for the elemental imaging of various commercial pharmaceutical drug and vitamin supplements.Specifically, elementalcomposition and heterogeneity are monitored for each different tablet. http://www.icdd.com/resources/axa/vol48/V48_37.pdf 11. Digital Imaging Digital imaging or digitalimage acquisition is thecreation of digital images,typically from a physicalscene. The term is often assumed toinclude the processing,compression, storage,printing, and display of suchimages. The most usualmethod is by digitalphotography with a digitalcamera.http://en.wikipedia.org/wiki/Digital_imaging 12. History Digital imaging wasdeveloped in the 1960s and1970s, largely to avoid theoperational weaknesses offilm cameras, for scientificand military missionsincluding the KH-11program.As digital technologybecame cheaper in laterCamera imaging system for leakdecades it replaced the olddetection in blister packsfilm methods for manypurposes.http://en.wikipedia.org/wiki/Digital_imaging 13. Applications Capturing Images of Culture Plates. To record positive QC results, many microbiologydepartments use either a standard or digital camera. Findings have to be recorded so that recommendationscan be backed up and decisions on the appropriatecourse of action are available for discussion betweenproduction managers and QC department personnel. Protecting pharmaceutical products againstcounterfeiting or identifying fraudulent import ofdonated or discounted drugs.http://en.wikipedia.org/wiki/Digital_imaging 14. Contd.QuantificationandCharacterization of Visibleand Sub-VisiblePharmaceutical Particles. The FlowCAM Series ofimaging particle analyzerscombine industry-leadingimage quality with automatedstatistical pattern recognitionsoftware to produce the mostpowerful sub-visible particleFlowCAManalyzer available for thepharmaceutical industry.http://www.fluidimaging.com/Collateral/Documents/English-US/Literature/Pharma_FlowCAM_Flyer_200ppi.pdf 15. Contd. Characterization ofparticle sizes in bulkpharmaceutical solidsusing digital imageinformation. Digital surface imagesof various granulebatches are capturedusing an inventiveoptical setup incontrolled illumination CAMSIZER- Digital Imaging -conditions. Particle Size/Shape Analyzerhttp://www.fluidimaging.com/Collateral/Documents/English-US/Literature/Pharma_FlowCAM_Flyer_200ppi.pdf 16. Imaging Techniques Terahertz Pulsed Spectroscopy In-Vitro Tomography Magnetic ResonanceImaging Near Infra-Red Spectral Imaging RamanSpectroscopy 17. Contd. Fluorescence correlation spectroscopy Micro-xray Fluorescence Hyperspectral Imaging Optical Coherence Tomography 18. Fluorescence CorrelationSpectroscopy Among the large number of optical methods thathave been developed for biological andchemical investigations, FCS plays the largestrole today, especially in the field of single-molecule analysis. Itbears not only a high intrinsic opticalefficiency, but also provides information aboutthe molecular environment and structure inmany different wayshttp://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html 19. History The history of the FCS is relatively long morethan 30 years. The idea of the FCS was proven in the beginningof 1970s by Cornell Univ. The recent boom of the FCS research beginningfrom the early 1990s had to wait the developmentof the electronics, computer, optics, and lasers. The first commercial instrument was released byZeiss in 1996.http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html 20. Principle FCSsystem uses a confocal microscope .He-Ne lasers, can be an excitation source of thefluorescence microscope. A pulsecompensator may be used to optimize theexcitation efficiency. A highnumerical aperture objective lens focusesthe excitation beam into the diffraction limitedspot, and effectively collects the fluorescencefrom the sample. http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html 21. Contd. A dicroic mirror separates the fluorescence from theexcitation beam and a long pass filter or aninterference filter passes appropriate wavelength offluorescence. The fluorescence spot is imaged on a small pinholeaperture. The fluorescence through the pinhole is focused againon a detector. An avalanche photo diode (APD) detector is used asthe photon counting detector.http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html 22. Schematic Diagram 23. Applications It is based on a computer-aidedspectrofluorimeter. When applied to pharmaceuticaldosage forms, Eg. it gives goodselectivity for a particular drug. Good calibration linearity,precision and recovery areobserved for both principal drugcomponents. This novel technique can providean improved method forgenerating diagnostic profiles ofdrugs, degradation products andmetabolites.http://www.sciencedirect.com/science/article/pii/S0003267000817249 24. Contd. Fluorescence detection and characterization has found awide use within biomedical research. For drug development activities in biotechnological andpharmaceutical industries. It is particularly heavily used in the pharmaceuticalindustry where it has almost completely replacedradiochemical labelling.http://www.sciencedirect.com/science/article/pii/S0003267000817249 25. Micro X-ray Fluorescence (MXRF) Micro-x-ray fluorescence(MXRF) isamong the newest technology used todetect fingerprints. It is a new visualization technique whichrapidly reveals the elemental compositionof a sample by irradiating it with a thinbeam of X-rays without disturbing thesample.http://en.wikipedia.org/wiki/Micro-X-ray_fluorescence 26. History It was discovered recently by scientists at the LosAlamos National Laboratory. The newly discovered technique was then firstrevealed at the 229th national meeting of theAmerican Chemical Society, the worlds largestscientific society.This new discovery could prove to be verybeneficial to the law enforcement world, becauseit is expected that MXRF will be able to detect themost complex molecules in fingerprints.http://en.wikipedia.org/wiki/Micro-X-ray_fluorescence 27. Principle When materials are exposed to short-wavelength X-rays , ionization of theircomponent atoms takes place. Ionization consists of the ejection ofelectrons from the atom. This expels tightly held electrons from theinner orbitals of the atom. The removal of an electron renders atomunstable, and electrons in higher orbitals"fall" into the lower orbital . In falling, energy is released in the form ofa photon,which is detected then.http://en.wikipedia.org/wiki/X-ray_fluorescence 28. ApplicationsThey 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 29. Contd. 3D micro-X-ray fluorescence analysis (3DXRF) is used for the non-destructive study ofpharmaceutical tablets.Measures the distribution of several inorganicelements (Zn, Fe, Ti, Mn, Cu) from the surfaceto a depth of several hundred microns under thesurface.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/ 30. Contd. MXRF can detect elemental composition for agiven sample by measuring its characteristic x-rayemission wavelengths or energies. Mesoscale ( > 10 m2) analysis is achievedthrough the use of a polycapillary focusing opticin conjunction with a Rh x-ray tube source. MXRF allows for simultaneous elemental analysiswith both quantitative and qualitative analysisof elements. It is a nondestructive technique and requiresminimal sample preparation. http://www.dxcicdd.com/04/PDF/T_Miller_1.pdf 31. Hyperspectral imagingSince the year 2000hyperspectral imagingsystems have beencommercially available formacroscopic andmicroscopic chemicalanalysis. Such a technique is highlyrelevant for pharmaceuticalindustry. Indeed, thehomogeneity of thedifferent components of atablet is an essential factorfor its quality. Hyperspectral Camerahttp://www.image-and-vision.com/Christelle_recherche_en.html 32. Principle The hyperspectral cameracollects both spatial and spectralinformation.Camera images one line of theproduct at a time and as thesample tray or product movesunderneath the camera , thewhole image is collected. A full spectrum of each point is Spectral signatures of generic tabletssaved, resulting in a "hypercube"of data that can be analyzed toidentify chemically distinctcomponents and their spatialdistribution within the product.http://www.middletonresearch.com/applications/hyperspectral-imaging-pharmaceutical.php 33. Applications Hyperspectral imaging, or chemicalimaging, is ideal for analyzing solidform pharmaceutical products such asfilms, blends, and tablets either duringon-line manufacturing or in laboratoryformulation development. By collecting spatial and spectral(chemical) information simultaneously,one can rapidly image a sample orproduct line.Hyperspectral Imager targets processmanufacturing Hyperspectral imaging providesinformation about the spatialdistribution of chemical componentswithin the sample.http://www.middletonresearch.com/applications/hyperspectral-imaging-pharmaceutical.php 34. Contd. The homogeneity or patterned dispersion of chemical components is known. Number oftablets 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?isAuthorized=no 35. Other applications Particle morphology and size distribution can be characterized bytechniques such as scanning electron microscopy (SEM) and X-raydiffraction (XRD) . Atomic force microscopy (AFM) has been used to study the effectsof mechanical processing on surface stability of pharmaceuticalpowders . Total reflection X-ray fluorescence (TXRF) has been used to studytrace elements Fourier transform near infrared (FT-NIR) methods have been usedto study the distribution of different organic ingredients in tabletswith a spatial resolution of ~20-100 m .http://www.icdd.com/resources/axa/vol48/V48_37.pdf 36. Terahertz pulsed spectroscopy Terahertz pulsedspectroscopy (TPS)and terahertz pulsedimaging (TPI) aretwo novel techniques. Usedfor the physicalcharacterization ofpharmaceutical drugmaterials and finalsolid dosage forms.http://ieeexplore.ieee.org/Xplore/login.jsp?url=http%3A%2F%2Fieeexplore.ieee.org%2Fiel5%2F19%2F4014679%2F04014688.pdf%3Farnumber%3D4014688&authDecision=-203 37. Schematic diagram 38. 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&authDecision=-203 39. In-vitro tomography Tomographyis 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 40. History It is only over the last fifteen years thattomography has been applied for the in-vitro characterisation of dosage forms. Tomographic imaging techniques offernew prospects for a better understandingof the quality, performance and releasemechanisms of pharmaceutical soliddosage forms. http://www.ncbi.nlm.nih.gov/pubmed/18778770 41. Principle It consist of passing X-rays andobtaining information with adetector on the other side. The X-raysource and the detectorare interconnected and rotatedaround the material to be imaged. Digital computers then assemblethe data that is obtained andintegrate it to provide a crosssectional image (tomogram) thatis displayed on a computerscreen. The image can be photographedor stored for later retrieval anduse.http://www.medindia.net/patients/patientinfo/CT_Scan_working.htm 42. TypesThere are several forms of tomography:- 1.Linear tomography: This is the most basic formof tomography. 2.Poly tomography: This was a complex form oftomography. With this technique, a number ofgeometrical 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).http://www.ncbi.nlm.nih.gov/pubmed/18778770 43. 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 ofAnalysis Inspections like Cracks, Porosities, Displacement, Quality Control http://www.ncbi.nlm.nih.gov/pubmed/18778770 44. 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 http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug- discovery-and-development.html 45. 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 46. 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.http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-discovery-and-development.html 47. Instrumentation The principal components are the magnet,radiofrequency (rf) coils and the gradient coils. The majority of MR systems use superconducting magnets. Most currently produced magnets are based onniobium-titanium (NbTi) alloys. The rf coils used to excite the nuclei usually arequadrature coils which surround the head orbody.http://www.informahealthcarebooks.com/in-vivo-mr-techniques-in-drug-discovery-and-development.html 48. Applications image analysis forassessment of HPMCmatrix tabletsstructural evolution inUSP Apparatus 4. MRI provides a meansDistribution of Mn2+ in the eye after 20to non-invasively and min of 3 mA transscleral iontophoresiscontinuously monitorapplied on the sclera next to the limbusocular drug-deliverysystems with a contrastagent .http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728085/figure/F3/ 49. Contd.Amphiphilichyperbranchedfluoropolymers asnanoscopic 19Fmagnetic resonanceimaging agentassemblies.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/ 50. Optical coherence tomography The enormous commercial potential of OCT is evidenced by aSeptember 2010 report from the Millennium Research Group(Toronto, ON, Canada). Optical coherence tomography (OCT) is a recently developedoptical technique that produces depth profiles of three-dimensionalobjects. It is a nondestructive interferometric method responding torefractive index variation in the sample under study and can reach apenetration depth of a few millimetres. OCT employs near-infrared (NIR) light and therefore provides alink between NIR spectroscopy and Terahertz (THz) measurementshttp://en.wikipedia.org/wiki/Optical_coherence_tomography 51. Schematic diagramhttp://www.laserfocusworld.com/articles/print/volume-47/issue-8/features/optical-coherence-tomography-oct-supports-industrial-nondestructive-depth-analysis.html 52. Applications The analysis ofpharmaceutical tablets andcoatings.It is also an attractivecandidate technology for in-line quality control duringmanufacturing. It allows rapid evaluation ofcoating properties, such asthickness and homogeneityindependently from variationsof the tablet core.http://iopscience.iop.org/0034-4885/66/2/204 53. Near-infrared spectral imaging Near-infraredspectroscopy (NIRS)is a spectroscopicmethod that uses thenear-infrared region ofthe electromagneticspectrum (from about800 nm to 2500 nm). Itsspectral range is0.7-5 microns andtemperature is 740-3000 degree kelvin.Near infrared imaging system: the Sapphire from Malvern companyhttp://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf 54. Principle NIR detects the presence ofdifferent chemical bonds,particularly O-H, N-H and C-H, by measuring opticalabsorption. Quartz halogen lamps providesource of illumination. Images are captured using atwo-dimensional array.Used in process quality control The array, eliminates the needto move the sample relative tothe detector.http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf 55. Schematic diagram 56. Applications In quality assurance ofpharmaceuticalproducts:analysis of tablets to assesspowder blend homogeneity. Modern NIR systems can beconfigured to study either asmall sample - a singlegranule,or a larger region,perhaps a complete blisterpack. This flexibility makes NIRTHE FOSS XDS based on NIR issuitable for high throughputMultiVial AnalyzerQA/QC applications as wellas in depth laboratory analysishttp://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf 57. 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.http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf 58. Contd. With NIR, granules can be investigated individually oras a complete dose. Imaging individual granules isbeneficial particularly for coated materials. Coating uniformity can therefore be quantitativelyassessed. API surface coverage can be measured directly byappropriately processing spectral data. Because the technique is non-destructive, the samesamples that have been analyzed using NIR-CI maysubsequently be subjected to dissolution testing. http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf 59. Raman Spectroscopy Ramanspectroscopy namedafter C. V. Raman.Used to studyvibrational,rotational, and otherlow-frequency modesin a system.http://en.wikipedia.org/wiki/Raman_spectroscopy 60. Principle It relies on inelastic scattering, orRaman scattering, ofmonochromatic light, usuallyfrom a laser in the visible, nearinfrared, or near ultraviolet range.The laser light interacts withmolecular vibrations, photons orother excitations in the system,resulting in the energy of thelaser photons being shifted up ordown.The shift in energy givesinformation about the vibrationalmodes in the systemhttp://en.wikipedia.org/wiki/Raman_spectroscopy 61. 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 Protectionhttp://www.renishaw.com/en/raman-spectroscopy-applications--6259 62. Contd. Polymorphism:ideal tool for the characterization of differentpolymorphic forms of active pharmaceutical ingredients (API) andexcipients. The ARAMIS and XploRA series are ideal forpolymorphic analysis. Blend Uniformity:Whether it is lab, scale-up or manufacturing,Raman probes enables monitoring of blending uniformity and endpoint detection. Exotic Formulations:The high spectral and spatial resolution ofconfocal Raman microscopes is critical in characterizing innovativedrug delivery systems such as stents, micro-needle patches, nano-carriers and others.http://www.renishaw.com/en/raman-spectroscopy-applications--6259 63. 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 tracecontamination, whether it is a foreign material orproduct degradation, helping root cause analysis issueswithin manufacturing processes and quality control. 64. Confocal laser scanningmicroscopy (CLSM) Means Light Amplification byStimulated Emission of Radiation.Phenomenon is brought aboutusing devices that transform lightof varying frequencies into a singleintense, nearly nondivergent beamof monochromatic radiation in thevisible region.The LSM 700 Laser Scanning Lasers operate in the visible,Microscope from Carl Zeissinfrared, or ultraviolet regions ofthe spectrum. They are capable of producingimmense heat and power whenfocused. http://www.xenogen.com/glossary.html 65. History Confocal microscopy was originally patented by Marvin Minsky in1957. In 1978, Thomas and Christoph Cremer designed a laser scanningprocess, which scans the three dimensional surface of an object. This CLSM design combined the laser scanning method with the 3Ddetection of biological objects labeled with fluorescent markers for thefirst time. During the next decade, confocal fluorescence microscopy wasdeveloped into a fully mature technology, in particular by groupsworking at the University of Amsterdam and the European MolecularBiology Laboratory (EMBL) in Heidelberg. http://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy 66. Principle In a confocal laser scanningmicroscope, a laser beam passesthrough a light source aperture.Then it is focused by an objectivelens on the surface of a specimen. Scattered and reflected laser lightfrom the illuminated spot is thenre-collected by the objective lens. A beam splitter separates off someportion of the light into thedetection apparatus. After passing a pinhole, the lightintensity is detected by aphotodetection device,transforming the light signal intoan electrical one that is recordedby a computer.http://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy 67. Schematic diagramhttp://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy 68. Applications The application of confocallaser scanning microscopy isin the physicochemicalcharacterisation ofpharmaceutical system. It is being exploited to study awide range of pharmaceuticalsystems, including phase-separated polymers, colloidalsystems, microspheres, pellets, Confocal Laser Scanningtablets, film coatings,Microscope for 300mm Waferhydrophilic matrices, andObservation/OLS3000-300chromatographic stationaryphases http://www.ncbi.nlm.nih.gov/pubmed/17945376 69. 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 distancethe coating droplets have to travel before impinging onto the coreparticles as a result of spray-drying of the coating droplets.2.Also, coating quality decreased with increasing viscosity of thecoating droplets, resulting in reduced spreading on the cores.http://www.ncbi.nlm.nih.gov/pubmed/19406233 70. Contd.In the examination of the embedment andthe release characteristics of chemicalpermeation enhancers from transdermaldrug delivery systems (TDDSs) of the"drug-in-adhesive" type. CLSMis demonstrated to be an excellenttool to study how enhancers areincorporated and diffuse into a TDDS.http://www.ncbi.nlm.nih.gov/pubmed/12049487 71. Photo Multiplier Tube (PMT) A vacuum phototube with additionalamplification by electronmultiplication . It consists of a photocathode, a seriesof dynodes, called a dynode chain onwhich a secondary- electronmultiplication process occurs, and ananode.Different types of dynode structureshave been developed, e.g. circularcage structure, linear focusedstructure, venetian blind structure,box and grid structurehttp://www.iupac.org/reports/V/spectro/partXI.pdf 72. History The photoelectric effect was carriedout in 1887 by Heinrich Hertz whodemonstrated it using ultravioletlight. Elster and Geitel two years laterdemonstrated the same effect usingvisible light striking alkali metals. Historically, the photoelectric effectis associated with Albert Einstein,who relied upon the phenomenon toestablish the fundamental principleof quantum mechanics, in 1905 forwhich Einstein received the 1921Nobel Prize.http://en.wikipedia.org/wiki/Photomultiplier 73. PhotoPrinciple Multipliertube Photomultipliers are constructed from a glass envelope thathouses a photocathode, several dynodes, and an anode. Incident photons strike the photocathode material. Electrons being produced as a consequence of thephotoelectric effect. These electrons are directed by the focusing electrode towardthe electron multiplier, where electrons are multiplied by theprocess of secondary emission. The electron multiplier consists of a number of electrodescalled dynodes. Each dynode is held at a more positivevoltage than the previous one. http://en.wikipedia.org/wiki/Photomultiplier 74. Contd. Upon striking the first dynode, more low energy electrons areemitted, and these electrons in turn are accelerated toward thesecond dynode. The geometry of the dynode chain is such that a cascadeoccurs with an ever-increasing number of electrons beingproduced at each stage. Finally, the electrons reach the anode, where the accumulationof charge results in a sharp current pulse indicating the arrivalof a photon at the photocathodehttp://en.wikipedia.org/wiki/Photomultiplier 75. Applications Mass Spectrometers Analysis of gas molecules by ionisingthe molecules,these ions are measuredby targeting them onto a dynode whichproduces a shower of electrons onto aphosphor screen viewed by aphotomultiplier. Particle Counting Many pharmaceutical and electronicsindustrial processes have to be carriedout in dust free conditions, a particlecounter is essential to monitor theamount of airborne particles. Light isscattered by the particles in a sampleand detected by a photomultiplier, the High-voltage Cascade Multiplier,amount of light scattered is Electrostatic Gun and its accessoriesproportional to the dust concentration.http://www.et-enterprises.com/photomultipliers/photomultiplier-applications 76. Contd. Liquid Scintillation Counting(LSC)Liquid scintillation counting iswidely used for the study ofbiological functions, tumours,viruses, and new drugs. Morefamously it is used forradioactive dating . Particle SizingThe size of particles in powders,sprays, and emulsions isimportant if they are to bemanufactured with the requiredproperties. Scattered laser lightis detected by a photomultiplier.http://www.et-enterprises.com/photomultipliers/photomultiplier-applications 77. Contd. LuminometersIts application in the food andpharmaceutical industries is growing.Example- inspecting products such as meatand cheese for the presence of antibiotics,drugs, insecticides. Radiation MonitoringMany people work in the nuclearpharmaceutical industry where they areexposed to radiation on a daily basis.Portable radiation meters incorporating aphotomultiplier and scintillator measure theradioactive dose received by these workersor detect radioactive contamination on theirgloves or clothes protecting them fromexceeding a safe level.http://www.et-enterprises.com/photomultipliers/photomultiplier-applications 78. Contd. SortingTransmitted or reflected light measuredby photomultipliers is the basis of manysorting and inspection techniques used inmanufacturing capsules. ChromatographyPhotomultipliers are used in instrumentswhich analyse chemical mixtures byseparating the constituents in a column.http://www.et-enterprises.com/photomultipliers/photomultiplier-applications 79. Contd. Spectrometry - fluorescenceThis technique is widely used for chemicalanalysis. A particular wavelength of lightfrom a Xenon lamp illuminates amolecular sample causing electrons to beexcited . These subsequently emit lightwhich is detected by a photomultiplier. X-ray DiffractometerPhotomultiplier tube (PMT) andmicroprocessor controlX-ray crystallography is the study of solidstructures by the diffraction of an intensebeam of x-rays. The angular pattern of x-rays produced is recorded by a radiationdetector, often a photomultiplier andscintillator assembly.http://www.et-enterprises.com/photomultipliers/photomultiplier-applications 80. TANDEM On-line TabletCharacterization PAT Tool TANDEM is an integrated, automated, on-linepharmaceutical tablet characterization toolproviding tablet weight, thickness, hardnessand NIR content uniformity analysis. Provides tablet weight, thickness, hardnessand NIR content uniformity analysis. Measures over 300 tablets per batch insteadof 10 by HPLC. Full validation with IQ/OQ/PQdocumentation and USP/EP protocols. Can be connected to any tablet presshttp://www.brukeroptics.com/tandem.html 81. Application TANDEM provides a comprehensivesolutions for the pharmaceutical industry.It provides a full set of tabletcharacterization parameters includingweight, size, thickness, hardness, diameterand NIR content uniformity in a singleanalyzer.The system consists of a BrukerMATRIX near infrared spectrometer, aDr. Schleuniger 10X-T tablet testingBruker MATRIX I FT-system, and a tablet handling unit. NIR SPECTROMETER TANDEM can be integrated with existingtablet pressing systems for automatedanalysis. http://www.brukeroptics.com/tandem.html 82. AcknowledgementI owe my thanks to Mrs.SHILPI AGARWAL forgiving me such a topic and guiding me. 83. Thank you