POLYMER PROPERTIES AND CHARACTERISATION

POLYMER PROPERTIES AND CHARACTERISATIONPRESENTED BYARCHANA S NAIRMPHARM PART IPHARMACEUTICS1

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CONTENTSIntroductionPropertiesMolecular weight determinationVibrational spectroscopyNuclear magnetic resonance spectroscopyMicroscopyThermal analysisX-ray diffraction methodsMechanical and rheological analysesConclusionReferences

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INTRODUCTIONPolymer means many parts.Use of polymer in drug delivery is guided by various properties like; molecular properties bulk properties Polymer characterization is the process of determining the size, structure and physical properties (such as thermal and mechanical properties) of polymeric materials.

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CRYSTALLINE AND AMORPHOUS POLYMERSIf the structure is linear, polymer chains can pack together in regular arrays.

For e.g.; polypropylene chains

With increased temperature, the crystal cells (crystallites) start to melt and the whole polymer mass suddenly melts at a certain temperature.

Amorphous structure is formed due to either rapid cooling of a polymer melt in which crystallization is prevented.4

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CRYSTALLINE AND AMORPHOUS POLYMERS

CrystallineOrdered

AmorphousRandom

Semi-crystallineConsists of both

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CRYSTALLINE AND AMORPHOUS POLYMERSPolymer strength and stiffness increases with crystallinity. With increase in crystallinity, the optical properties of a polymer are changed.Crystallinity increases the barrier properties of a polymer packaging.Crystallinity topology and isomerism, molecular weight, intermolecular forces, rate of cooling etc.Anisotropy.

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THERMAL TRANSITIONSVolume of a polymer can change with temperature as first or second order transition.Tm first order thermal transition.Tg second order thermal transition.

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GLASS TRANSITION TEMPERATURE

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GLASS TRANSITION TEMPERATURE

Rigid glass state soft rubber state.100C to above 300C.Important in solid dosage form.Tg of a polymer depend on many factors, length of polymer chain, side chain group. polymer chain flexibility. polymer chain branching, polymer chain cross linking. processing rate, plasticizers.

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GLASS TRANSITION TEMPERATURE

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GLASS TRANSITION Vs MELTINGGlass TransitionMeltingProperty of the amorphous regionBelow Tg: Disordered amorphous solid with immobile moleculesAbove Tg: Disordered amorphous solid in which portions of molecules can wiggle aroundA second order transition

Property of the crystalline regionBelow Tm: Ordered crystalline solidAbove Tm: Disordered meltA first-order transition 12

Techniques of Tg measurementDifferential scanning calorimetryRefractive indexDynamic mechanical measurementsSpecific heat measurementsThermo mechanical analysis Thermal expansion measurementMicro-heat-transfer measurementIsothermal compressibilityHeat capacity Elastic modulus or hardnessBroad-line NMR

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IMPROVED PROCESSING AND HANDLING QUALITIES SPRAY DRYING

Non-sticky and sticky products. Sticky products - difficult to spray dry. Remain as syrup or stick on the dryer wall, or form unwanted agglomerates in the dryer chamber and conveying system . Mainly due to the low glass transition temperature (Tg) of the low molecular weight sugars present in such products, essentially sucrose, glucose, and fructose.For bulky side groups-T g is higher 14

GLASS TRANSITION IN SPRAY DRYING

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IMPROVED DISSOLUTION AND BIOAVAILABILITYIndomethacin & nifedipine are poorly water soluble drugs exhibiting dissolution rate limited oral bioavailability.Both are prepared as glass solutions.Glass solutions showed increased drug dissolution rate than crystalline forms of drugs.16

VISCOELASTIC PROPERTIESNeither a pure elastic nor a pure fluid material.Have ability to store energy and to dissipate it.Viscoelastic materialsEg: PVC Creep test , polymer is rst loaded with a certain weight and its deformation is then monitored over the time. Stress relaxation test, polymer is rst deformed to a certain extent, and then its stress relaxation is monitored with the time.

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CREEP TESTUsing a tensile specimen to which a constant stress is applied, often by the simple method of suspending weights from it.

Surrounding the specimen is a thermostatically controlled furnace, the temperature being controlled by a thermocouple attached to the gauge length of the specimen.

The extension of the specimen is measured by very sensitive extensometer, results of the test are then plotted on a graph of strain versus time to give a curve .

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STRESS RELAXATION TEST Determine a sample's creep properties when subjected to a prolonged tensile or compressive load at a constant temperature. The rate of deformation of a sample to stress at a constant temperature is known as the creep rate. It is the slope created by the creep vs. time.If creep recovery is measured, the test will determine the stress-relaxation - the rate of decrease in deformation that takes place when the load is removed.

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MECHANICAL PROPERTIESPolymers resist differently when they are stressed.

Can resist against stretching, compression, bending, sudden stress, and dynamic loading.

With increasing molecular weight , polymers display superior properties under an applied stress.

Flexible polymer can perform better under stretching whereas a rigid polymer is better under compression.

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MECHANICAL PROPERTIES

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MOLECULAR WEIGHTAverage molecular weight-Fundamental characteristic of a polymer sample.Controls the function of biomedical polymers.Pure sample contain molecules differing only in degree of polymerization.Molecular weight may be a) Number averaged molecular weight b) Weight averaged molecular weight c) Viscosity averaged molecular weight d) z-averaged molecular weight

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MOLECULAR WEIGHT

d) Viscosity average molecular weight23

NUMBER AVERAGE MOLECULAR WEIGHTThe number average molecular weight(Mn) is the statistical average molecular weight of all the polymer chains in the sample.

Mn can be predicted by polymerization mechanisms.

Measured by methods that determine the number of molecules in a sample of a given weight; for example, colligative methods such as end-group assay.24

WEIGHT AVERAGE MOLECULAR WEIGHTMolecular weight of a chain in determining contributions to the molecular weight average.

The more massive the chain, the more the chain contributes to Mw.

Mw is determined by methods that are sensitive to the molecular size rather than just their number, such as light scattering techniques.25

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VISCOSITY AVERAGE MOLECULAR WEIGHTThe molecular weight of the polymer is measured by using viscometer and the molecular weight obtained by this technique is called viscosity average molecular weight.

From the Mark-Houwink equation the relationship among the molecular weight and viscosity are given below

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Z- AVERAGED MOLECULAR WEIGHTMz is especially sensitive to the presence of high molecular weight chains.

Mz may be determined directly by sedimentation equilibrium(ultracentrifugation) & light scattering.

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TECHNIQUES TO DETERMINE MOLECULAR WEIGHTMethodsMeasured ParameterM.Weight MeasuredUpper Limit(g per mole)

Membrane osmometryOsmotic pressure of polymer solventMn5x10Light scattering (LS)Intensity of light scattered by dilutepolymer solutionsMw, Mz1x10 Gel permeationchromatography (GPC)Elution volume of the polymersolution through a GPC columnpacked with porous microparticlesMn , Mw1 x 108ViscometryFlow time of polymer solutionthrough a capillaryM v1 x 108

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MOLECULAR WEIGHTThe molecular weight of polymers can be determined by a number of physical and chemical methodsLight scatteringGel permeation chromatography (GPC)Viscometry

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LIGHT SCATTERINGRayleigh scattering.

Additional scattering shows presence of solute molecules, this may be a function of the concentration, as well as their size and shape.

By measuring differences in intensity of scattered light, averaged size of polymer solutes and their molecular weights can be determined.

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LIGHT SCATTERING

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GEL PERMEATION CHROMATOGRAPHY

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VISCOMETRY33

VISCOMETRY

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VIBRATIONAL SPECTROSCOPY INFRARED AND RAMAN SPECTROSCOPYAt low temperatures, a molecule will exist in its ground vibrational state and will be excited to a higher vibrational state if radiant energy is absorbed.E is related to the frequency of radiation () absorbed, and the relationship is given by, E = hThe spectral transitions are detected by scanning through the entire IR frequency.

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VIBRATIONAL SPECTROSCOPY INFRARED AND RAMAN SPECTROSCOPYThe energies of molecular vibrations of interest for analytical work mostly correspond to wavelengths in the range 2.5 to 25 m.

Results in identication of the functional groups and the modes of their attachment to the polymer backbone.

Characterize the polymers molecular and material structure.

Eg: Determination of level of amine groups in chitosan.

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VIBRATIONAL SPECTROSCOPY INFRARED AND RAMAN SPECTROSCOPY

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RAMAN SPECTROSCOPYDetects the inelastic scattering of photons by molecules.Provide a fingerprint by which molecules can be identified. Used to observe vibrational, rotational, and other low-frequency modes in a system.The laser light interacts with molecular vibrations,photonsor 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.

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RAMAN SPECTROSCOPYStokes shift.

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RAMAN SPECTROSCOPY

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NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY Microstructure and chain conguration of polymers, both in solution and in the solid state. Identication of certain atoms or groups in a polymer molecule as well as their positions relative to each other can be obtained by one-, two- and three-dimensional NMR spectra . When a strong external magnetic eld is applied to material containing nuclei possessing property of spin, behave like bar magnets -orientate themselves in two energy states, a low-energy state & a high-energy state.

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NUCLEAR MAGNETIC RESONANCE SPECTROSCOPYThe transition of a nucleus from one energy state to another occurs if a discrete amount of energy is absorbed from an electromagnetic radiation. E = hV = 2H0

If the resonance frequency for all nuclei of the same type in a molecule were identical, only one line or peak would be observed.

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NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

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MICROSCOPYCharacterization of polymer material ultrastructure. Used to examine the detailed shape, size and distribution of polymeric micro and nanoparticles, and their interactions with biological environments. These include traditional optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and scanning probe microscopy (SPM).

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OPTICAL MICROSCOPYMicrostructural information with a resolution on the order of 1 m. Imaging is carried out using both reected and transmitted light. If the absorption coefficient varies regionally within a sample, when a beam of light travels through such a sample, contrasting regions of intensity will be obtained in the nal image. For a specimen that can be prepared as a thin lm, by casting on the microscope slide, examination using transmitted light is most useful

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OPTICAL MICROSCOPYTwo common are polarized-light microscopy and phase-contrast microscopy. Former exploits the ability of crystalline materials to rotate the plane of polarized light. Structure of polymer liquid crystals may also be studied using polarizing microscopy. Reected-light microscopy - topographical features of solid polymer materials.

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SCANNING ELECTRON MICROSCOPY SEM is very valuable electron microscopy technique with a resolution of about 5 nm.

A ne beam of electrons is scanned across the surface of an opaque specimen, and an appropriate detector collects the electrons emitted from each point.

An image having a great depth of eld and a remarkable three-dimensional appearance is built up line by line.

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SCANNING ELECTRON MICROSCOPY To produce stable images, the specimen is usually coated with a conducting lm prior to examination.

The typical lm thickness is about 20 nm.

Coating materials can give a high secondary electron yield and thus increase image contrast.

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TRANSMISSION ELECTRON MICROSCOPYInvolves transmitting a beam of electrons instead of light through a sample in a high-vacuum environment. Images and associated contrasts arise from regional differences in electron densities. Resolution of about 1 to 100 nm. Specimen needs to be very thin in order to transmit electron beams through the sample.Specimens are placed on copper grids or carbon-coated copper grids and viewed through the holes in the grid.

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TRANSMISSION ELECTRON MICROSCOPYReplication, heavy-metal staining, are widely used to increase image contrast.

Rapidly adjusted to provide electron diffraction pattern from a selected area, facilitating the investigation of crystal structure and orientation and particular morphological features to be identied.

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TRANSMISSION ELECTRON MICROSCOPY

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TRANSMISSION ELECTRON MICROSCOPY

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SCANNING PROBE MICROSCOPYWhen a probe tip is brought very close to a surface, the physical phenomenon, may be exploited to produce a three-dimensional topographical image of the surface. The resolution is at the nanometre level. The most popular scanning probe microscopy (SPM) techniques include scanning tunnelling microscopy (STM) atomic force microscopy (AFM). AFM operates by measuring attractive or repulsive forces between a tip and the sample surface, and can image samples both in air and in liquids.54

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SCANNING TUNNELLING MICROSCOPY Imaging surfaces at the atomic level.STM is based on the concept of quantum tunnelling.A conducting tip is brought very near to a metallic semi conducting surface, a bias between two can allow electrons to tunnel through vacuum between them.Variations in the tunnelling current as the probe passes over the surface are translated in to an image.

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SCANNING TUNNELLING MICROSCOPY

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ATOMIC FORCE MICROSCOPY57

THERMAL ANALYSISStructure dependent physical properties of the polymer are measured as a function of temperature or time, while a polymer is subjected to a controlled temperature program. The most common techniques are Differential scanning calorimetry (DSC), Thermal gravimetry (TG), Dynamic mechanical analysis (DMA). Used to identify and characterize both polymers and drug-loaded polymeric delivery systems.58

DIFFERENTIAL SCANNING CALORIMETRY Whenever a polymer undergoes a phase transition, temperature tends to remain constant while energy is taken into the system. Differences between the energy acquired or released as a function of temperature or time while subject to a controlled temperature rise.Useful for recording thermal transitions such as the glass transition temperature Tg, melt temperature Tm, and degradation or decomposition temperature TD. Used to characterize the liquid crystal state of organization and other forms of self-assembly.

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THERMAL GRAVIMETRY Used to measure the change in weight of a polymer sample while it is heated, using a sensitive balance.

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DYNAMIC MECHANICAL ANALYSIS Properties of a polymer are studied as it goes through a time-dependent mechanical change.Analytical technique is able to give important information on polymer relaxation processes and phase morphologies. Useful method for identifying segmental and side-chain motion within a chain and can also be used to study copolymers and polymer blends.It is most useful for studying the viscoelastic behaviour ofpolymers.

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X-RAY DIFFRACTION METHODS Useful method for investigating arrangements of atoms or molecules within a material. If there is an orderly arrangement of substructures within a material with repeat distances of a similar magnitude to the wavelength of light used (0.050.25 nm), interference patterns are produced. Such patterns provide information on the geometry of polymer structures. Two methods used are Wide-angle x-ray scattering (WAXS) Small-angle x-ray scattering (SAXS).

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WAXSDistance from sample to the detector is shorter and diffraction maxima at larger angles are observed.Degree of crystallinity of polymer samples. Sample is scanned in a wide-angle X-ray goniometer, and the scattering intensity is plotted as a function of 2 angle. Crystalline solid consists of regularly spaced atoms (electrons) that can be described by imaginary planes. Distance between these planes is called the d-spacing.

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SAXSValue of angles used is from 1o to 5o. Useful in detecting large periodicities from 5 to 70 nm in a structure such as lamellae or distribution of particles or voids in materials.64

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MECHANICAL AND RHEOLOGICAL ANALYSES It is a reection of the polymers molecular properties. Carried out in order to establish if the polymer is t for the purpose. Tensile properties of solid polymers can be characterized by their deformation behaviour. Rubbery polymers - lower modulus or stiffness. Glass and semi crystalline polymers - higher moduli and lower extensibility. 66

MECHANICAL AND RHEOLOGICAL ANALYSES Used to obtain information related to the ow behaviour of polymer melts and polymer solutions.

Capillary and rotational rheometers.

Polymer uids are non-Newtonian in behaviour, mostly being shear- thinning or pseudoplastic.

Viscoelasticity is a unique property of certain polymers, which display both viscous- and elastic-type behaviour at ordinary temperatures and loading rates.Useful way of assessing hydrogels

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CONCLUSIONPolymer materials have been used for the administration of pharmaceuticals & play an important role in fabrication of various controlled release and drug targeting systems.The use of a polymer for drug delivery is controlled by its molecular properties. Considering the polymers functional properties, it is important that adequate polymer characterization is available. Many methods available for the characterization of polymers.

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REFERENCESAlfred martin. Physical pharmacy; (4): 556-92Alan.R.Katritzky, Sulev Sild. Quantitative structure property relationship correlation of glass transition temperature of high molecular weight polymers: Journal of Chemical Information and Modeling;Feb 1998(2):300-304P. Debye. Molecular weight determination by light scattering.The Journal of Physical Chemistry;Jan 1947,51(1):18-3269

REFERENCESA.W Craig, D.A Henderson. A viscometer for dilute polymer solutions. Journal of polymer science; Jan 1956,Vol 10:124-32

Heinz.W.Siesler. Vibrational spectroscopy of polymers. International Journal for Polymer Analysis and Characterization; Nov 2011,8(16)

Swee Chye Yeo, A. Eisenberg. Advancement in Modern polymer Technology Journal of Applied Polymer Science; April 1977,21(4): 875-898

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