sumit ppt

Thermal analytical techniques: 

Thermal analytical techniques Presented by: SUMIT KUMAR MITTAL I.S.F. COLLEGE PF PHARMACY, MOGA (PUNJAB) M.PHARMA (QUALITY ASSURANCE) Ist SEMESTER 1

HISTORY OF THERMAL ANALYSIS **In 1945, Dr. Erhard Mettler, a Swiss engineer, founded a precision mechanics company, which ultimately became the now renowned METTLER TOLEDO company. **He laid the foundation for the successful balance business and invented the substitution principle with a single-pan balance. In 1973, the company introduced the first electronic balance with electromagnetic force compensation. **Dr. Mettler also strongly promoted thermal analysis. **In the early 1960s, Dr. Hans-Georg Wiedemann, an East German scientist, convinced him to combine the advanced weighing technology with a furnace in order to measure weight changes as a function of temperature. : 

HISTORY OF THERMAL ANALYSIS ** In 1945, Dr. Erhard Mettler , a Swiss engineer, founded a precision mechanics company, which ultimately became the now renowned METTLER TOLEDO company. ** He laid the foundation for the successful balance business and invented the substitution principle with a single-pan balance. In 1973, the company introduced the first electronic balance with electromagnetic force compensation. ** Dr. Mettler also strongly promoted thermal analysis. ** In the early 1960s, Dr. Hans-Georg Wiedemann , an East German scientist, convinced him to combine the advanced weighing technology with a furnace in order to measure weight changes as a function of temperature. 2

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3 WHAT IS THERMAL ANALYSIS Thermal method of analysis is, a group of technique in which physical property of a substance or its reaction products is measured as a function of temperature while the substance is subjected to controlled temperature program .

Thermal analysis:: 

Thermal analysis: Useful for both qualitative and quantitative purposes. It is utilized for determining physical and chemical properties of APIs, Polymers, circuit boards, geological material sand coals. It is preferable techniques for measuring transition temperatures, weight losses, energies for transitions, dimentional changes, modulus changes, and viscoelastic properties. The techniques include the measurement of temperatures at which changes occur, the measurement of energy absorbed(endothermic transition) or evolved (exothermic transition) during phase transition or a chemical reaction, and the assessment of physical changes resulting from changes in temperature. 4

Types of thermal analytical techniques:: 

Types of thermal analytical techniques: S.No . Technique Quantity Measured Applications 1. DSC (differential scanning calorimetry) Heat and temperature of transitions and reactions Reaction kinetics, purity analysis and polymer curves 2. DTA (differential thermal analysis) Temperature of transition and reactions Phase diagrams, thermal stability 3. TGA (thermo- gravimetric analysis) Weight change Thermal stability, compositional analysis 4. TMA (thermo-mechanical analysis) Dimension and viscosity change Softening temperatures, Expansion coefficients 5. EGA (evolved gas analysis) Amount of gaseous products of thermally induced reactions Analysis of volatile organic components of shale 5

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6 • Differential Scanning Calorimetry (DSC)– Measure heat absorbed or liberated during heating or cooling, In this, the measurement of differences in energy required to maintain the sample and reference at an identical temperature. The sample and reference are maintained at the same temperature, even during a thermal event . • Differential Thermal analysis (DTA) -Measure temperature difference between the sample and reference. • Thermal Gravimetric Analysis (TGA)– Measure change in weight during heating or cooling • Thermomechanical Analysis (TMA) – Measure change in dimensions during heating or cooling

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7 Basic Principles of Thermal Analysis Modern instrumentation used for thermal analysis usually consists of four parts: 1)sample/sample holder 2)Sensors or transducer to detect/measure a property of the sample (A Thermocouple / Balance / Displacement transducer / Gas detector: to measure the heat flow {DSC } or a temperature {DTA} or a balance to monitor the weight changes TG) 3)an enclosure within which the experimental parameters may be controlled DTA power compensated DSC heat flux DSC

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8 Differential scanning calorimetry : Definitions: A calorimeter measures the heat into or out of the sample. A differencial calorimeter mearures the heat of a sample relative to a reference. A differential scanning calorimeter does all of the above heats the sample with a linear temperature rate. Endothermic heat flows into the sample. Exothermic heat flows out of the sample.

1. Differential scanning calorimetry:: 

1. Differential scanning calorimetry: When a material is heated or cooled, there is a change in its structure or composition. This transformation are connected with a heat exchange. DSC is used for measuring the heat flow into and out of the sample, as well as for determining the thermal phenomena during a controlled change in temperature. Widely used thermal analysis method because of its simplicity, speed and availability. These measurement provide quantitative and qualitative information about physical and chemical changes that envolve endothermic and exothermic process, or changes in heat capacity. 9

METLER TELEDO (DSC) APPARATUS: 

METLER TELEDO (DSC) APPARATUS 10

DSC GRAPH: 

DSC GRAPH For 1 st order transitions such as melting, crystallization, sublimation, boiling, etc., of the curve gives the energy involved in the transition. For 2 nd order transition the signal gives the change in the specific heat, for example, glass transition. Melting, boiling and sublimation are endothermic, which means they need energy. Crystallization is exothermic, which means that it supplies energy. Desolations without melting are generally endothermic Solid phase transition and decomposition may be endothermic or exothermic 11

DSC Graph: 

DSC Graph 12

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N 2 flow Pt thermopile Sample Reference Pt thermopile T 1 T 2 heater heater D W Schematic of DSC Instrument

Types of DSC:: 

Types of DSC: Two main types: a) Power compensated DSC b) Heat flux DSC c) Modulated DSC 14

a) Power compensated DSC:: 

a) Power compensated DSC: The temperatures of the sample and reference are controlled independently using separate, identical furnaces . The temperatures of the sample and reference are made identical by varying the power input to the two furnaces; the energy required to do this is a measure of the enthalpy or heat capacity changes in the sample relative to the reference . 15

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16 Power compension DSC sample holder •Al or Pt pans Sensors •Pt resistance thermocouples •separate sensor sand heaters for the sample and reference Furnace •separate blocks for sample and reference cells temperature controller •differential thermal power is supplied to the heaters to maintain the temperature of the sample and reference at the program value

b) Heat flux DSC: : 

b) Heat flux DSC: In this, the sample and reference are connected by a low resistance heat flow path & the assembly is enclosed in a single furnace. Enthalpy or heat capacity changes in the sample cause a difference in its temperature relative to the reference; the resulting heat flow is small compared with that in differential thermal analysis (DTA) because the sample and reference are in good thermal contact. The temperature difference is recorded and related to enthalpy change in the sample using calibration experiments. 17

Heat Flux DSC: 

Heat Flux DSC 18 Sample holder •sample and reference are connected by a low-resistance heat flow path •Al or Pt pans placed on constantan disc Sensors •chromel ®- constantan thermocouples (differential heat flow) •chromel ®-a lumel thermocouples (sample temperature) f urnace •one block for both sample and reference cells temperature controller •the temperature difference between the sample and reference is converted to differential thermal power, dD q / dt , which is supplied to the heaters to maintain the temperature of the sample and reference at the program value

Modulated DSC (MDSC): 

Modulated DSC (MDSC) i ntroduced in 1993; “heat flux” design Modulated DSC heating profile Sinusoidal (or square wave or Saw tooth)modulation is Superimposed on the underling heating rate. Total heat flow signal contains all of the thermal transition of standard DSC Fourier Transformation analysis is used to separate the total heat flow in to its two component. 19

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20 DSC Calibration baseline •evaluation of the thermal resistance of the sample and reference sensors Measurements over the temperature range of interest 2-step process •the temperature difference of two empty crucibles is measured •the thermal response is then acquired for a standard material, usually sapphire or indium, on both the sample and reference platforms •amplified DSC signal is automatically varied with temperature to maintain a constant calorimetric sensitivity with temperature

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21 Sample Preparation •accurately-weigh samples(~3-20mg) •small sample pans(0.1mL) of inert or treated metals ( Al, Pt, Ni, etc.) •several pan configurations, e.g., open, pinhole, or hermetically-sealed(air-tight-vacuum sealing) pans •the same material and configuration should be used for the sample and the reference •material should completely cover the bottom of the pan to ensure good thermal contact •avoid over filling the pan to minimize thermal lag from the bulk of the material to the sensor * small sample masses and low heating rates increase resolution, but at the expense of sensitivity Al Pt Alumina Ni Cu Quartz

impure substances •melting characterized at peak maxima : 

impure substances •melting characterized at peak maxima Melting Processes by DSC DSC GRAPH Pure substances •linear melting curve •melting point defined by onset temperature Melting with decomposition •exothermic •endothermic 22

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Best Practices of Thermal Analysis • small sample size •good thermal contact between the sample and the temperature-sensing Device •proper sample encapsulation •starting temperature well below expected transition temperature •slow scanning speeds •proper instrument calibration •use purge gas (N2 or He) to remove corrosive off-gases •avoid decomposition in the DSC

Properties DSC can measure:: 

Properties DSC can measure: Glass transitions Melting and boiling points Crystallization time and temperature Percent Crystallinity Heats of fusion and reactions Specific heat capacity Oxidative/thermal stability Reaction kinetics Purity 24

Sources of errors:: 

Sources of errors: Calibration Contamination Sample preparation – how sample is loaded into a pan Residual solvents and moisture. Thermal lag Heating/Cooling rates Sample mass Processing errors 25

Applications of DSC:: 

Applications of DSC: Glass transition temperatures( Tg ) Crystallinity and crystallization rate Reaction kinetics: Exothermic reactions are readily monitored. Here the determination of rate of release of heat release, dH / dt is used to determine the extent of reaction as a function of time. Determination of water content in pharmaceutical hydrate. DSC is the general method for determining the purity and heat of fusion of high purity organic chemicals. Compatibility studies between ibuproxam and pharmaceutical excipients Compatibility studies b/w mannitol and omeprazole sodium isomers 26

2.Differential Thermal Analysis: 

2.Differential Thermal Analysis It is a calorimetric technique recording the temperature and heat flow associated with thermal transitions in a material. This enables phase transitions to be determined (e.g. melting point, glass transition temperature, crystallization etc.). The temperature program involves heating the sample & reference material in such a way that the temperature of the sample T­ s increases linearly with time and the difference in temperature Tis then monitored and plotted against sample temperature to give a differential thermogram . 27

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Differential Thermal Analysis DTA involves heating or cooling a test sample and an inert reference sample under identical conditions Recording of any temperature difference between the sample and reference. This differential temperature is then plotted against time, or against temperature. Changes in the sample which lead to the absorption or evolution of heat can be detected relative to the inert reference. 28

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29 The reference material should have the following characteristics It should undergo no thermal events over the operating temperature range It should not react with the sample holder or thermocouple Both the thermal conductivity and heat capacity of the reference should be similar to those of the sample. Alumina, aluminum trioxide and carborundum , etc., have been extensively used as reference materials for inorganic samples, while for organic compounds, especially polymers, use has been made of octyl phthalate and silicone oil. A common technique for matching the thermal properties of the sample to those of the reference, is to use the reference material as a diluents for the sample. There must obviously be no reaction of the sample with the reference material

DTA Thermogram:: 

DTA Thermogram: 30

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Instrumentation:: 

Instrumentation: Sample holder : sample & reference cells(Al) Sensors: Pt /Rh or chromel / alumel thermocouples one for the sample and one for the reference joined to differential temperature controller Furnace: alumina block containing sample and reference cells Temperature controller: controls for temperature program and furnace atmosphere sample pan inert gas vacuum reference pan heating coil alumina block Pt/ Rh or chromel / alumel thermocouples 32

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33 Differential Thermal Analysis 1.DTA involves heating or cooling a test sample and an inert reference under identical conditions, while recording any temperature difference between the sample and reference. 2.This differential temperature is then plotted against time, or against temperature. 3.DTA can therefore be used to study thermal properties and phase changes which do not lead to a change in enthalpy. 4.The baseline of the DTA curve should exhibit discontinuities at the transition temperatures and the slope of the curve at any point will depend on the micro structural constitution at that temperature. 5.A DTA curve can be used as a finger print for identification purposes. 6.The area under a DTA peak can be to the enthalpy change of the sample .

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36 Factors affecting DTA Results: BY INSTURMENT: Furnace Atmosphere Size&Shape of the furnace Sample holder Material Sample holder geometry Heating rate speed & Response of recording device thermocouple location BY SAMPLE: Particlesize Thermal conductivity Heat capacity Packing density Amount of Sample swelling or shrinkage of sample degree of crystallinity

Advantages: : 

Advantages: DTA instruments can be used at very high temperatures I nstruments are highly sensitive F lexibility in crucible volume/form Characteristic transition or reaction temperatures can be accurately determined 37

Applications:: 

Applications: Widely used tool for studying and characterizing polymers. Widely used in ceramics and metal industry where it is used to study decomposition temperatures, phase transitions, melting and crystallization points and thermal stability. Most important application is the generation of phase diagrams and the study of phase transitions. Simple and accurate way of determining the melting, boiling and decomposition points of organic compounds. 38

3.Thermo gravimetric Analysis(TGA):: 

3.Thermo gravimetric Analysis(TGA): Thermo gravimetric analysis (TGA) is a thermal analysis technique which measures the weight change in a material as a function of temperature and time, in a controlled environment. This can be very useful to investigate the thermal stability of a material, or to investigate its behaviour in different atmospheres (e.g. inert or oxidizing). It is suitable for use with all types of solid materials, including organic or inorganic materials. 39

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40 TGA TGA is a technique in which the mass of a substance is measured as a function of temperature, while the substance is subjected to a controlled temperature programme . “Controlled temperature programme ” can mean: •heating and/or cooling at a linear rate (by far commonest) •isothermal measurements •combinations of heating, cooling and isothermal stages •other, more modern approaches, in which the temperature profile is modified according to the behaviour of the sample.

Instrumentation:: 

Instrumentation: 41

METLER TELEDO (TGA) APPARATUS: 

METLER TELEDO (TGA) APPARATUS 42

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Parts of instrument:: 

Parts of instrument: Analytical balance: H ighly sensitive, and capable of providing quantitative information about samples ranging in mass from 1mg to 100g but usually balance used has a range of 5-20mg. Furnace : temperature range is from ambient to 1500 0 C while cooling and heating rate is 1-200 0 C . Purging gas system : Nitrogen/argon are usually used to purge the furnace and prevent oxidation of the sample. 44

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45 Thermogravimetric Analysis (TGA) • Reflection type: in this the light beam is deflected when there is change in the mass and imbalance in the photodiode is measured in form of current and is amplified and fed in the coil which is insulated between the magnetic field which restores the beam in its actual position. The amplified photodiode current is monitored and transformed in to mass loss information to data acquisition system.

Typical TGA curves:: 

Typical TGA curves: No change. Desorption/drying. Single stage decomposition. Multistage decomposition. Same as 4 but no intermediates/ heating rate is too high. Atmospheric reactions As 6 but product decomposes at higher temperature. 46

Advantages of TGA:: 

Advantages of TGA: Any type of solid can be analysed, with minimal sample preparation (e.g. powders, pellets, chunks, flakes etc.). Minimum sample size ( at least 0.1mg ). Qualitative or quantitative analysis. Limitations : Solid (or initially solid) samples only. Data interpretation not always straightforward. 47

Uses of TGA/DTA:: 

Uses of TGA/DTA: Thermal stability/degradation investigation of organic or inorganic materials, e.g.  polymers, composites, glasses, metals, minerals etc. Thermal stability/degradation investigations in inert or oxidative atmospheres, or in vacuum. Determination of organic/inorganic content of mixtures. Chemical composition measurements (using appropriate reference standards, accurate quantification of sample composition can be determined). Phase transition measurement (e.g. glass transition, clustering, Crystallinity, melting point ). Reaction kinetics with reactive gases (e.g., oxidation, hydrogenation, chlorination, adsorption/desorption ). 48

4.Thermo mechanical analysis(TMA):: 

4.Thermo mechanical analysis(TMA): Thermo mechanical analysis (TMA) provides measurement of penetration, expansion, contraction, and extension of materials as function of temperature. 49

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50 Thermo Mechanical Analysis Volume is a fundamental thermodynamic quantity. Thermal expansivity is a useful engineering quantity: = ( dL / dt )/Lo Thermomechanical Analysis (TMA) is the study of the relationships between a sample’s length (volume) and its temperature .

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51 Thermo Mechanical Analysis Thermo mechanical analysis (TMA) is one of the important characterization techniques in the field of thermal analysis. With TMA, the dimensional properties of a sample are measured as the sample is heated, cooled or held under is other mal conditions. The loading or force applied to the sample can be varied with TMA.

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52 The probe is connected to the transformer named as linear variable differential transformer (LVDT). The core is connected to the quartz probe that contains the thermocouple for the measurement of the sample temperature. Weight tray can be attached to the upper end of the probe to determine the predetermined force.

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Instrumentation: The sample sits on a support within the furnace. Resting upon it is a probe to sense changes in length, normally a Linear Variable Displacement Transducer (LVDT). The probe and support are made from a material such as quartz glass which has a low, reproducible, and accurately known coefficient of thermal expansion A thermocouple near the sample indicates its temperature. There is usually provision for establishing a flowing gas atmosphere through the instrument, to prevent oxidation for example, and also to assist in heat transfer to the sample. Helium is effective in this respect. The load may be applied by static weights, as above, or by a force motor. This latter method gives the advantage that the applied load can be programmed to allow a greater range of experiments. Sample sizes are commonly around 5-10mm in height and width. It is important to prepare samples with clean, flat and parallel faces to avoid artifacts in the recorded curves. 53

Instrumentation: 

Instrumentation 54

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55 TMA probe types With the TMA technique, a number of different probe configurations are offered in order to optimize the test conditions for a specific sample and/or application. The TMA probes can be of different types such as expansion, penetration, compression, flexure type. The most commonly used TMA probe is the expansion probe. This probe rests on the surface of the test specimen under low loading conditions. As the sample expands, during heating, the probe is pushed up and the resulting expansion of the sample is measured.

TMA probe types: 

TMA probe types 56

Applications:: 

Applications: It is used to determine thermal coefficient of linear samples. It is used to determine the viscoelastic properties of polymer. It is used to determine the hardness of resins. It is used to determine expansion and contraction behavior of different fibers. Analysis of bio-adhesive polymers. Purity control analysis of calcium and disodium Fostomycin. 57

Applications of the TMA: 

Applications of the TMA 58

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59 Evolved gas analysis Evolved gas analysis (EGA) is a method used to study the gas evolved from a heated sample that undergoes decomposition or desorption. It is possible to detect which gas is evolved using evolved gas detection (EGD) EGD is often performed by coupling EGA with mass spectrometry, Fourier transform spectroscopy, gas chromatography, or Optical In-Situ Evolved Gas Analysis. By coupling the thermal analysis instrument, e. g. TGA (Thermogravimetry) or DSC (Differential scanning calorimetry , with a fast Quadrupole Mass Spectrometer (QMS) the detection of gas separation and identification of the separated components are possible in exact time correlation with the other thermal analysis signals.

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60 evolved gas analysis(instrument)

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61 ROLE IN PHARMACEUTICAL INDUSTRY Thermal methods are one of the fundamental tool available to pharmaceutical scientist and have been widely used for many years for characterization of pharmaceutical material. For characterization of drug substances, excipients , packaging material, polymorphism. Method for development of dosage form design: -Choice of salt form. - Drug substance- excipient interaction 3. (MTDSC) is used characterize polymeric material in order to predict the possible drug interaction.

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62 4 . Hydrate stability of pharmaceutical ingredient 5. To check the purity of the formulation as indicated by difference in melting point of pure sample and the formulation. -IMPORTANCE IN FOOD INDUSTRY- Alterations in temperature affect the physical and chemical properties of food so food analyst checks it through various thermal methods.

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63 IMPORTANCE IN MEDICAL FIELD- Usefull in understanding transitions in the skin and drug penetration in the skin . Ability of thermoanalytical technique to provide information of alteration in biological system is not only important in medical research but also in advanced patient care.

NEW ADVENTURES IN THERMAL ANALYSIS: 

NEW ADVENTURES IN THERMAL ANALYSIS 64 MICROTHERMAL ANALYSIS -It combines thermal analysis with atomic force microscopy (AFM). It is actually a scanning thermal microscopic technique in which thermal properties of surface are measured as function of temperature and used to produce images.

References:: 

References: Skoog, Holler, Nieman; “Principles of instrumental analysis”; Books/Cole publication, Fifth edition, page no. 798-808. Willard, Merritt, Dean; “Instrumental methods of analysis”, CBS publication, Seventh edition, Page no. 761-784. Dean; “Deans’ analytical chemistry handbook”, Tata McGraw-Hill publication, Second edition, page no. 15.1-15.17 Q. M. Craig; Mike Reading “Thermal analysis of pharmaceutical”, CRC Press. 65

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THANK YOU 66