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PHARMACEUTICAL IMAGING TECHNIQUESPRESENTED TO:        PRESENTED BY:Mrs.Shilpi Agarwal   Sakshi Taneja                     ...
Definition   The visual representation of an object, such as a body    part or pharmaceutical product, for the purpose of...
History    1895 – Roentgen discoverd x-rays    1896 - Edison created fluoroscope    1896 - Bequerel discovered radioact...
TypesChemical    ImagingBiophotonic ImagingElemental ImagingMolecular ImagingDigital   Imaging
Chemical Imaging forPharmaceutical Testing   Chemical imaging is a non-destructive    imaging technique that combines spa...
History Commercially availablelaboratory-based chemical imaging systems emerged in the early 1990s. Initially used      ...
Principle Chemical imaging shares the  fundamentals of vibrational spectroscopic  techniques. Vibrational spectroscopy m...
Applications Content   and Blend Uniformity in granulation    mass during tablet manufacture. Characterization and Ident...
Elemental Imaging    The analysis of the distribution of    pharmaceutical materials in tablet    formulations, such as d...
ApplicationsMXRF    was is for the elemental imaging of various commercial pharmaceutical drug and vitamin supplements.S...
Digital Imaging   Digital imaging or digital    image acquisition is the    creation of digital images,    typically from...
History   Digital imaging was    developed in the 1960s and    1970s, largely to avoid the    operational weaknesses of  ...
Applications   Capturing Images of Culture Plates.   To record positive QC results, many microbiology    departments use...
Contd.    Quantification    andCharacterization of Visible    and Sub-Visible    Pharmaceutical Particles.   The FlowCAM...
Contd.   Characterization of    particle sizes in bulk    pharmaceutical solids    using digital image    information.  ...
Imaging Techniques Terahertz Pulsed   Spectroscopy In-Vitro Tomography Magnetic Resonance      Imaging Near   Infra-Re...
Contd. Fluorescence correlation spectroscopy Micro-xray Fluorescence Hyperspectral   Imaging Optical Coherence Tomogra...
Fluorescence CorrelationSpectroscopy Among   the large number of optical methods that  have been developed for biological...
History   The history of the FCS is relatively long more    than 30 years.   The idea of the FCS was proven in the begin...
Principle FCS    system uses a confocal microscope .    He-Ne lasers, can be an excitation source of the    fluorescence...
Contd.   A dicroic mirror separates the fluorescence from the    excitation beam and a long pass filter or an    interfer...
Schematic Diagram
Applications   It is based on a computer-aided    spectrofluorimeter.   When applied to pharmaceutical    dosage forms, ...
Contd.   Fluorescence detection and characterization has found a    wide use within biomedical research.   For drug deve...
Micro X-ray Fluorescence (MXRF)   Micro-x-ray fluorescence(MXRF) is    among the newest technology used to    detect fing...
History   It was discovered recently by scientists at the Los    Alamos National Laboratory.   The newly discovered tech...
Principle   When materials are exposed to short-    wavelength X-rays , ionization of their    component atoms takes plac...
Applications    They are able to analyze     coating thicknesses and     changes in composition     as a function of coat...
Contd.   3D   micro-X-ray fluorescence analysis (3D      XRF) is used for the non-destructive study of      pharmaceutica...
Contd. MXRF can detect elemental composition for a  given sample by measuring its characteristic x-ray  emission waveleng...
Hyperspectral imaging    Since the year 2000    hyperspectral imaging    systems have been    commercially available for ...
Principle   The hyperspectral camera    collects both spatial and spectral    information.    Camera images one line of ...
Applications   Hyperspectral imaging, or chemical    imaging, is ideal for analyzing solid    form pharmaceutical product...
Contd.     The   homogeneity or       patterned dispersion of       chemical components       is known.     Number of   ...
Other applications   Particle morphology and size distribution can be characterized by    techniques such as scanning ele...
Terahertz pulsed spectroscopy Terahertz   pulsed    spectroscopy (TPS)    and terahertz pulsed    imaging (TPI) are    tw...
Schematic diagram
Applications      To characterize crystalline properties of       drugs and excipients.      Different polymorphic forms...
In-vitro tomography Tomography    is the method of imaging a single plane, or slice, of an object resulting in a tomogram...
History   It is only over the last fifteen years that    tomography has been applied for the in-    vitro characterisatio...
Principle   It consist of passing X-rays and    obtaining information with a    detector on the other side.   The X-rays...
TypesThere are several forms of tomography:- 1.Linear tomography: This is the most basic form  of tomography. 2.Poly tomog...
Industrial applications   Fault detection and failure analysis   Assembly inspection of complex mechanisms   Dimensiona...
Magnetic resonance imaging Magnetic Resonance (MR) imaging is one of the principal modalities imaging of the samples at h...
Principle    MRI uses magnets to polarise     and excite hydrogen in water     molecules .    The MRI machine emits an  ...
contd. The pulse makes the protons in that area absorb the energy needed to make them spin in a different direction.  Th...
Instrumentation   The   principal components are the magnet,      radiofrequency (rf) coils and the gradient coils.   Th...
Applications   image analysis for    assessment of HPMC    matrix tablets    structural evolution in    USP Apparatus 4....
Contd.Amphiphilichyperbranchedfluoropolymers asnanoscopic 19Fmagnetic resonanceimaging agentassemblies.It is a useful te...
Optical coherence tomography   The enormous commercial potential of OCT is evidenced by a    September 2010 report from t...
Schematic diagramhttp://www.laserfocusworld.com/articles/print/volume-47/issue-8/features/optical-coherence-tomography-oct...
Applications   The analysis of    pharmaceutical tablets and    coatings.    It is also an attractive    candidate techn...
Near-infrared spectral imaging Near-infrared  spectroscopy (NIRS)  is a spectroscopic  method that uses the  near-infrare...
Principle   NIR detects the presence of    different chemical bonds,    particularly O-H, N-H and C-    H, by measuring o...
Schematic diagram
Applications   In quality assurance of    pharmaceutical      products:    analysis of tablets to assess    powder blend ...
Contd.    Assessing the impact of processing conditions on moisture     content- Hydroxyl groups are strong NIR absorbers...
Contd.   With NIR, granules can be investigated individually or    as a complete dose. Imaging individual granules is    ...
Raman Spectroscopy Raman    spectroscopy named    after C. V. Raman.    Used to study    vibrational,    rotational, and...
Principle   It relies on inelastic scattering, or    Raman scattering, of    monochromatic light, usually    from a laser...
Applications    Polymorph control    Content uniformity    Blend uniformity    Rapid composition analysis    Exotic f...
Contd.   Polymorphism:ideal tool for the characterization of different    polymorphic forms of active pharmaceutical ingr...
Contd. Particle Size Analysis: Sizes of particle is critical in determining bio-availability. Raman microscopes can deter...
Confocal laser scanning    microscopy (CLSM)   Means Light Amplification by    Stimulated Emission of Radiation.    Phen...
History   Confocal microscopy was originally patented by Marvin Minsky in    1957.   In 1978, Thomas and Christoph Creme...
Principle   In a confocal laser scanning    microscope, a laser beam passes    through a light source aperture.    Then ...
Schematic diagramhttp://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy
Applications   The application of confocal    laser scanning microscopy is    in the physicochemical    characterisation ...
Contd. Using CLSM the importance of setting up the     appropriate distance between the coating nozzle     and the powder...
Contd.    In the examination of the embedment and    the release characteristics of chemical    permeation enhancers from...
Photo Multiplier Tube (PMT)   A vacuum phototube with additional    amplification by electron    multiplication .   It c...
History   The photoelectric effect was carried    out in 1887 by Heinrich Hertz who    demonstrated it using ultraviolet ...
PhotoPrinciple                                                       Multiplier                                           ...
Contd. Upon striking the first dynode, more low energy electrons are  emitted, and these electrons in turn are accelerate...
Applications   Mass Spectrometers     Analysis of gas molecules by ionising    the molecules,these ions are measured    b...
Contd.   Liquid Scintillation Counting    (LSC)    Liquid scintillation counting is    widely used for the study of    bi...
Contd.   Luminometers    Its application in the food and    pharmaceutical industries is growing.    Example- inspecting ...
Contd.   Sorting    Transmitted or reflected light measured    by photomultipliers is the basis of many    sorting and in...
Contd.   Spectrometry - fluorescence    This technique is widely used for chemical    analysis. A particular wavelength o...
TANDEM On-line Tablet    Characterization PAT Tool   TANDEM is an integrated, automated, on-line    pharmaceutical tablet...
Application   TANDEM provides a comprehensive    solutions for the pharmaceutical industry.    It provides a full set of...
AcknowledgementI owe my thanks to Mrs.SHILPI AGARWAL for      giving me such a topic and guiding me.
Thank you
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Pharmaceutical imaging techniques (2)

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  1. 1. PHARMACEUTICAL IMAGING TECHNIQUESPRESENTED TO: PRESENTED BY:Mrs.Shilpi Agarwal Sakshi Taneja M.Pharm 1st year ISF College Of Pharmacy MOGA,PUNJAB
  2. 2. 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
  3. 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. 4. TypesChemical ImagingBiophotonic ImagingElemental ImagingMolecular ImagingDigital Imaging
  5. 5. Chemical Imaging forPharmaceutical Testing Chemical imaging is a non-destructive imaging technique that combines spatial and spectral information to provide a more complete characterization of a samplehttp://www.gatewayanalytical.com/industris-served/pharmaceutical/industry-leaeding-chemical-imaging-experts
  6. 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. 7. 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. http://en.wikipedia.org/wiki/Chemical_imaging
  8. 8. 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 http://en.wikipedia.org/wiki/Chemical_imaging
  9. 9. 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
  10. 10. 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. http://www.icdd.com/resources/axa/vol48/V48_37.pdf
  11. 11. 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
  12. 12. 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.http://en.wikipedia.org/wiki/Digital_imaging
  13. 13. 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. http://en.wikipedia.org/wiki/Digital_imaging
  14. 14. 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
  15. 15. 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
  16. 16. Imaging Techniques Terahertz Pulsed Spectroscopy In-Vitro Tomography Magnetic Resonance Imaging Near Infra-Red Spectral Imaging Raman Spectroscopy
  17. 17. Contd. Fluorescence correlation spectroscopy Micro-xray Fluorescence Hyperspectral Imaging Optical Coherence Tomography
  18. 18. Fluorescence CorrelationSpectroscopy 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
  19. 19. 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. http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html
  20. 20. 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. http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html
  21. 21. 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. http://bppc03.es.hokudai.ac.jp/~gnishi/fcs/fcs.html
  22. 22. Schematic Diagram
  23. 23. 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
  24. 24. 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
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. 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/
  30. 30. 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
  31. 31. 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 Camerahttp://www.image-and-vision.com/Christelle_recherche_en.html
  32. 32. 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
  33. 33. 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
  34. 34. 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?isAuthorized=no
  35. 35. 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 . http://www.icdd.com/resources/axa/vol48/V48_37.pdf
  36. 36. 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%2F19%2F4014679%2F04014688.pdf%3Farnumber%3D4014688&authDecision=-203
  37. 37. Schematic diagram
  38. 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. 39. 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
  40. 40. 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. http://www.ncbi.nlm.nih.gov/pubmed/18778770
  41. 41. 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
  42. 42. TypesThere 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). http://www.ncbi.nlm.nih.gov/pubmed/18778770
  43. 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 of Analysis Inspections like Cracks, Porosities, Displacement, Quality Control http://www.ncbi.nlm.nih.gov/pubmed/18778770
  44. 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. 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. 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. 47. 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
  48. 48. 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/
  49. 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. 50. 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
  51. 51. Schematic diagramhttp://www.laserfocusworld.com/articles/print/volume-47/issue-8/features/optical-coherence-tomography-oct-supports-industrial-nondestructive-depth-analysis.html
  52. 52. 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
  53. 53. 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 companyhttp://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf
  54. 54. 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.http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf
  55. 55. Schematic diagram
  56. 56. 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 analysishttp://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf
  57. 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. 58. 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. http://www.pharmpro.com/PDFs/0908/chemicalimaging.pdf
  59. 59. 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
  60. 60. 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
  61. 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. 62. 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
  63. 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. 64. 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
  65. 65. 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
  66. 66. 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. http://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy
  67. 67. Schematic diagramhttp://en.wikipedia.org/wiki/Confocal_laser_scanning_microscopy
  68. 68. 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 http://www.ncbi.nlm.nih.gov/pubmed/17945376
  69. 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 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. http://www.ncbi.nlm.nih.gov/pubmed/19406233
  70. 70. 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. http://www.ncbi.nlm.nih.gov/pubmed/12049487
  71. 71. 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
  72. 72. 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
  73. 73. PhotoPrinciple 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. http://en.wikipedia.org/wiki/Photomultiplier
  74. 74. 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 http://en.wikipedia.org/wiki/Photomultiplier
  75. 75. 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
  76. 76. 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 .http://www.et-enterprises.com/photomultipliers/photomultiplier-applications
  77. 77. 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. http://www.et-enterprises.com/photomultipliers/photomultiplier-applications
  78. 78. 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. http://www.et-enterprises.com/photomultipliers/photomultiplier-applications
  79. 79. 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. http://www.et-enterprises.com/photomultipliers/photomultiplier-applications
  80. 80. 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
  81. 81. 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
  82. 82. AcknowledgementI owe my thanks to Mrs.SHILPI AGARWAL for giving me such a topic and guiding me.
  83. 83. Thank you
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