Thermal analysis ppt.ppt pharmaceutical analysis

Analysis

1. Thermal Analysis Chalapathi Institute of Pharmaceutical Sciences

2. Thermal analysis Definition: Thermal analysis (TA) is a group of techniques that study the properties of materials as they change with temperature. Types of Thermal analysis: TGA (Thermal Gravimetric analysis) DTG (Derivative Thermo Gravimetry) DTA (Differential Thermal Analysis) DSC ( Differential Scanning Calorimetry) TT ( Thermometric Titrimetry) DMA (Dynamic Mechanical Analysis) TMA (Thermo Mechanical Analysis)

3. Differential scanning calorimetry

4. History of DSC: The technique was developed by E. S. Watson and M. J. O'Neill in 1962 , introduced commercially in 1963 at Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. First a differential scanning calorimeter that could be used in Biochemistry was developed by P.L.Privalov in 1964. Definition:  Differential scanning Calorimetry is a thermoanalytical technique in which, the difference in the amount of heat required to increase the temperature of a sample and reference is measured as a function of temperature.

5. Advantages: Instruments can be used at very high temperatures. Instruments are highly sensitive. Characteristic transition or reaction temperatures can be determined. Flexibility in sample volume. High resolution obtained. Stability of the material. Disadvantages: DSC generally unsuitable for two-phase mixtures. Difficulties in test cell preparation in avoiding evaporation of volatile solvents. DSC is generally only used for thermal screening of isolated intermediates and products. Very sensitive to any changes. Uncertainty of heats of fusion and transition temperatures.

6. Pri nciple: It is a technique in which the energy necessary to establish a zero temperature difference between the sample & reference material is measured as a function of temperature. Here, sample & reference material are heated by separate heaters in such a way that their temperature are kept equal while these temperature are increased or decreased linearly. During heating two types of reactions can be take place one is the endothermic and the other is the exothermic. Endothermic reaction: If sample absorbs some amount of heat during phase transition then reaction is said to be endothermic. In endothermic reaction more energy needed to maintain zero temperature difference between sample & reference. Ex: Melting, boiling, sublimation, vaporization, de-solvation.

7. Exothermic reaction: If sample released some amount of heat during phase transition, then reaction is said to be exothermic. In exothermic reaction, less energy needed to maintain zero temperature difference between sample & reference. Ex: Crystallization, degradation, polymerization. DSC is widely used to measure glass transition temp & characterization of polymer. Glass Transition temp (Tg): Temperature at which an amorphous polymer or an amorphous part of crystalline polymer goes from hard brittle state to soft rubbery state.

8. Instrumentation: 1.Heat flux DSC: • In heat flux DSC, the difference in heat flow into the sample and reference is measured while the sample temperature is changed at the constant rate. • The main assembly of the DSC cell is enclosed in a cylindrical, silver heating block, which dissipates heat to the specimens via a constant an disc which is attached to the silver block. • The disk has two raised platforms on which the sample and reference pans are placed. • A chromel disk and connecting wire are attached to the underside of each platform, and the resulting chromel constantan thermocouples are used to determine the differential temperatures of interest. • Alumel wires attached to the chrome discs provide the chromel-alumel junctions for independently measuring the sample and reference temperature.

9. Heat flux DSC • A separate thermocouple embedded in the silver block serves a temperature controller for the programmed heating cycle. An inert gas is passed through the cell at a constant flow rate of about 40 ml/min .

10. 2 . Power compensation DSC : In power compensation DSC, the temperatures of the sample and reference are kept equal to each other while both temperatures are increased or decreased linearly. The power needed to maintain the sample temperature equal to the reference temperature is measured. In power compensation DSC two independent heating units are employed. These heating units are quite small, allowing for rapid rates of heating , cooling and equilibration. The heating units are embedded in a large temperature- controlled heat sink The sample and reference holders have platinum resistance thermometers to continuously monitor the temperature of the materials. Both sample and reference are maintained at the programmed temperature by applying power to the sample and reference heaters.

11. The instrument records the power difference needed to maintain the sample and reference at the same temperature as a function of the programmed temperatures Power compensated DSC has lower sensitivity than heat flux DSC , but its response time is more rapid. This makes power compensated DSC well suited for kinetics studies in which fast equilibrations to new temperature settings are needed. it is also capable of higher resolution then heat flux DSC. All power compensated DSC are in basic principles the same. But, one of the special power compensated DSC is photo DSC. Where direct measurements of radiation flow occur under a light source.

12. Power compensation DSC

13. Experimental Parameters: 1. Sample preparation 2. Experimental conditions 3. Calibration 4. Resolution 5. Sources of errors

14. 1.Sample Preparation: Sample Types: The DSC can be used to analyze virtually any material that can be put into a DSC sample pan. This includes: • Films • Fibers • Powders • Solutions • Composites When making quantitative measurements or verifying reproducibility, it is important to ensure good thermal contact between the sample and sample pan. The physical characteristics of the sample affect the quality of this contact.

15. When using powdered or granular samples, spread them evenly across the bottom of the pan to minimize thermal gradients . For solid samples, select the side of your sample with the flattest surface for contact with the pan. After encapsulating the sample, ensure that the pan bottom is flat. If it is not, flatten it by pressing the pan bottom on a flat surface . NOTE: The oils on your fingers can affect the results of thermal analysis experiments. If you overfill a pan, the heating or cooling procedures may cause the sample to boil out or explode the pan. If you are using an Auto-sampler and this occurs so that the Autosampler cannot remove a pan from the cell because of deformation or boiled-out material, operation is halted until the problem is corrected. Therefore, you should be reasonably familiar with the effects of heating and cooling procedures on your samples and pans.

16. Determining sample size: Normally, sample weight in DSC experiments is in the range of 5 to 20 milligrams. If purity determinations are to be performed, then sample sizes of 1 to 3 milligrams are recommended. Refer to the table below to guide you when selecting the sample size and heating rates for your experiment.

17. Selecting a sample pan: Selection of the appropriate DSC sample pan and lid is a very important element of your method development process. The results you obtain from the use of DSC will be affected by your choices.

18. Selecting a sample pan:

19. 2. Experimental conditions Heating Rate Samples are heated at a rate of 10 or 20 °C/min in most cases. Lowering the heating rates is known to improve the resolution of overlapping weight losses. Advances in the technology have made it possible for variable heating rates (High Resolution TGA) to improve resolution by automatically reducing the heating rate during periods of weight loss.

20. 3. DSC Calibration (a). 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, on both the sample and reference platforms

21. (b). T emperature: • Goal is to match the melting onset temperatures indicated by the furnace thermocouple readouts to the known melting points of standards analyzed by DSC • Should be calibrated as close to the desired temperature range as possible. • Heat flow :use of calibration standards of known heat capacity, such as sapphire, slow accurate heating rates (0.5 – 2.0 ° C/min), and similar sample and reference pan weights.

22. One of the most important performance characteristics of a DSC instrument is its resolution. This refers to the ability of the DSC to separate or resolve closely occurring thermal transitions. The resolution of a DSC cell is dependent upon its particular design properties including the mass of the furnace, the temperature measuring system employed and the response time of the cell. The resolution of a DSC is also a function of the given experimental conditions, including:  Purge gas  Sample mass  Heating rate Enhanced resolution can be obtained using a helium rather than a nitrogen, air or oxygen purge, due to the significantly higher thermal conductivity of helium. Lower sample masses can provide improved resolution over larger masses. Slower heating rates will yield significantly better resolution than faster rates. 4. Resolution:

23. 5. 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

24. Applications: Metal alloy melting temperatures and heat of fusion. Metal magnetic or structure transition temperatures and heat of transformation. Intermetallic phase formation temperatures and exothermal energies. Oxidation temperature and oxidation energy. Exothermal energy of polymer cure (as in epoxy adhesives), allows determination of the degree and rate of cure. Determine the melting behavior of complex organic materials, both temperatures and enthalpies of melting can be used to determine purity of a material. Measurement of plastic or glassy material glass transition temperatures or softening temperatures, which change dependent upon the temperature history of the polymer or the amount and type of fill material, among other effects.

25. Determines crystalline to amorphous transition temperatures in polymers and plastics and the energy associated with the transition. Crystallization and melting temperatures and phase transition energies for inorganic compounds. Oxidative induction period of an oil or fat. May be used as one of multiple techniques to identify an unknown material or by itself to confirm that it is the expected material. Determine the thermal stability of a material. Determine the reaction kinetics of a material. Measure the latent heat of melting of nylon 6 in a nylon Spandex fabric to determine the weight percentage of the nylon.

26. Differential Thermal Analysis

27. Defi nition: Ø Differential thermal analysis is a technique in which the temperature difference between the sample and a thermally inert reference substance is continuously recorded as a function of temperature or time. Ø Differential thermal analysis is also known as thermography. Advantages: Ø Instruments can be used at very high temperatures. Ø Instruments are highly sensitive. Ø Characteristic transition or reaction temperatures can be accurately determined. Disadvantages: Ø Uncertainty of heats of fusion. Ø Transition or reaction estimations is 20-50% DTA.

28. Principle: Differential thermal analysis involves the technique of recording the difference in temperature between a substance and a reference material against either time or temperature as the two specimens are subjected to identical temperature regimens in an environment heated or cooled at a controlled rate. Thus, a differential thermogram consists of a record of the differences in sample and reference temperature (differential temperature, ΔT) plotted as a function of time t, sample temperature (T s ), reference temperature (T r ) or furnace temperature (T f ). Sharp endothermic peaks give ideas of changes in crystallinity or fusion process whereas broad endotherms signify dehydration reactions. Physical changes give rise to endothermic curves whereas chemical reactions (particularly those of an oxidative nature) give rise to exothermic peaks.

29. Endothermic reaction (absorption of heat) includes sublimation and gives downward peak. Exothermic reaction (liberation of heat) includes oxidation, polymerization and gives upward peak. DTA allows the detection of every physical or chemical change whether or not it is accompanied by a change in weight.

30. Instrumentation:

31. 1. Furnace: DTA apparatus always prefer a tubular furnace. This is constructed with an appropriate material (wire or ribbon) wound on a refractory tube. Such furnaces possess the desired characteristics for good temperature regulation and programming. These are fairly inexpensive. 2. Sample holder: Both metallic as well as nonmetallic materials are employed for the fabrication of sample holders. Metallic materials generally include nickel, stainless steel, platinum and its alloys. Non-metallic material generally include glass, vitreous silica or sintered alumina. Metallic holders give rise to sharp exotherms and flat endotherms. On the other hand non-metallic holders yield relatively sharp endotherms and flat exotherms. Cylindrically geometry is used.

32. 3. DC amplifier: It is used for amplification of signals obtained from thermocouple. It is gain and low noise circuit. 4. Temperature controller and Recorder:
a). Temperature control: The three basic elements are required to control temperature are sensor, control element and heater. There are two methods for controlling temperature. These are i). On-off control: If the sensor signal indicates that the temperature has become greater than the set point, the heater is turned off. This type of control is not widely used in DTA. Inexpensive.

33. ii). Proportional control: Heat input to the system is progressively reduced as the temperature approaches the desired value. These are widely used in DTA instruments. But in expensive DTA instrument elegant electronic controllers are used. b). Temperature programming: A desired rate of heating or cooling and to maintain the constant temperature at any desired value, thermal apparatus requires a time dependent temperature cycling of the furnace. This can be achieved by employing a temperature programmer which transmits a certain time based instructions to the control unit. DTA instrument because one cannot achieve linear rate of heating or cooling. However, one can achieve linearity in the rate of heating or cooling if the autotransformer is driven in a non-linear fashion using a special cam-drive.

34. c). Recorder: The signals obtained from the sensors can be recorded in which the signal trace is produced on paper or film, by ink, heating stylus, electric writing or optical beam. There are two types. i. Deflection type: The recording pen is moved directly by the input signal. ii. Null type: The input signal is compared with a reference or standard signal and the difference is amplified and used to adjust the reference signal through a servo motor until it matches the input signal.

35. 5. Thermocouples: In DTA and TG instruments temperature sensors are thermocouples. The voltage signal produced between the two hetero-junctions of the thermocouple depends upon the temperature difference between these two junctions. While selecting the thermocouple as the temperature sensor, one has to consider the following points: Temperature interval. Thermoelectric coefficient. Chemical compatibility with the sample Chemical gaseous environment used and reproducibility of the EMF vs temperature curve as function of thermal cycling. Availability and cost.

36. Thermocouples made from chromel P and alumel wires (both nickel-chromium alloys) are used to measure and control temperature up to 1100 C in air. Above 1100 C, one should use thermocouples made from pure platinum-rhodium alloy wires. 6. Cooling device: The cooling system is considered as separate from the temperature programmer because in most instruments cooling is completely independent from heating. A simple automatic cooling system is effective in DTA instrument.

37. Applications: 1. Polymeric materials: DTA useful for the characterization of polymeric materials in the light of identification of thermo physical, thermo chemical, thermo mechanical and thermo elastic changes or transitions. 2. Measurement of crystalline: Measurement of the mass fraction of crystalline material in semi crystalline polymers. 3. Identification of substance: DTA curve for two substances are not identical. Therefore, these serve as finger prints for various substances. Practically, DTA has become an established technique for the identification of clays. 4. Identification of products: When a substance reacts with another substance, the products are identified by their specific DTA curves. Therefore, this technique has been termed as reaction DTA technique.

38. 5. Melting points: As melting points can be easily determined by DTA, it means that this can be used as a direct check of the purity of the compound. 6. Quantitative analysis: We know that the area of DTA peak is proportional to the total heat of reaction and hence to the weight of the sample. Therefore, the quantitative analysis is possible with the help of standard curves of peak area vs weight. 7. Analysis of biological materials: DTA curves are used to date bone remains or to study archaeological materials.