Thermal Techniques By Aman Kumar Mahto

Different types of Thermal Techniques and its applications

1. THERMAL TECHNIQUES BY :- AMAN KUMAR MAHTO M.PHARM (1 ST SEMESTER) PHARMACEUTICAL CHEMISTRY Presentation Date : 30/10/2018

2. THERMAL TECHNIQUES Thermal Techniques or Thermal Analytical Techniques - are group of techniques in which a property of a sample is monitored against temperature (or time), while the temperature of the sample in a specified atmosphere is programmed .[by ICTAC] These methods are used for analytical purpose hence the word Thermal Analysis is used more often. 30-10-2018 JAMIA HAMDARD (SPER) 2

3. OBJECTIVES Studying the behaviour of pharmaceuticals by different thermal analysis instruments, under different conditions and then comparing the results is another objective. Common applications used in thermal analysis incorporate the categorization of the physicochemical attributes of crystalline solids and the discovery and classification of polymorphic forms . Differential techniques are used to review kinetics in the solid-state, which includes accelerated stability study , decomposition and the aging effects on various formulations . 30-10-2018 JAMIA HAMDARD (SPER) 3

4. Principle parts of Thermal Analysis Thermal analysis usually consists of the following parts: Sample holder /compartment for the sample. Sensors to detect/measure a property of the sample and the temperature. An enclosure within which the experimental parameters (temperature, rate, environment) may be controlled. A computer to control data collection and processing . 30-10-2018 JAMIA HAMDARD (SPER) 4

5. Thermal analysis types 30-10-2018 JAMIA HAMDARD (SPER) 5

6. THERMAL ANALYSIS TYPES Differential Scanning Calorimetry (DSC) Measure heat absorbed or liberated during heating or cooling Differential Thermal Analysis (DTA) They are use for thermal investigation where thermal change can be observed and characterised Thermal Gravimetric Analysis (TGA) Measure change in weight during heating or cooling 30-10-2018 JAMIA HAMDARD (SPER) 6

7. Thermal transitions Glass transition temperature Crystallization temperature Melting temperature 30-10-2018 JAMIA HAMDARD (SPER) 7

8. DIFFERENTIAL SCANNING CALORIMETRY (DSC) 30-10-2018 JAMIA HAMDARD (SPER) 8

9. Differential Scanning Calorimetry Principle : DSC measures differences in the amount of heat required (i.e., heat-flow) to increase the temperature of a sample and a reference as a function of temperature. A DSC consists of a cell , which is the heart of a DSC. The cell is connected with a gas inlet through which different gas are purged depending on the data required. Based on the DSC cells there are two primary types: HEAT FLUX POWER COMPENSATION 30-10-2018 JAMIA HAMDARD (SPER) 9

10. Types of DSC instrument Heat Flux DSC Routine applications Near / at line testing in harsh environment Automated operation Cost-sensitive laboratories Power Compensation DSC High resolution / high sensitivity research studies Absolute specific heat measurement Very sensitive to contamination of sample holders Heat flux DSC Power compensation DSC 30-10-2018 JAMIA HAMDARD (SPER) 10

11. Heat flux DSC (Hf-DSC) This consists of a large single furnace which acts as an infinite heat sink to provide or absorb heat from the sample. The key components are the sample pan (typically an aluminium pan and lid) which is combined with the reference pan (always the same material as the sample pan, aluminium). Nitrogen is the most common gas used but alternate inert gas is helium or argon. The heat flux DSC is based in the change in temperature D T between the sample and reference. 30-10-2018 JAMIA HAMDARD (SPER) 11

12. Hf-DSC curve 30-10-2018 JAMIA HAMDARD (SPER) 12

13. Power compensation (Pc-DSC) Small individual furnaces use different amounts of power to maintain a constant DT between sample and reference and the advantage here include faster heating and cooling , and better resolution . This type of cell, with two individually heated with platinum heater, monitors the difference between the sample and reference. Platinum resistance thermometers track the temperature variations for the sample and reference cells. Holes in the compartment lids allow the purge gas to enter and contact the sample and reference. 30-10-2018 JAMIA HAMDARD (SPER) 13

14. Instrumentation of DSC 30-10-2018 JAMIA HAMDARD (SPER) 14

15. DSC graph . 30-10-2018 JAMIA HAMDARD (SPER) 15

16. Experimental parameters Sample preparation Experimental conditions Calibration Heating and cooling rates Resolution Source of errors 30-10-2018 JAMIA HAMDARD (SPER) 16

17. Sample preparation Accurately weighed samples (3-20mg, usually 3-5mg for simpler powders). Small sample pans (0.1 mL) of inert or treated metals (Al, Pt). Several pan 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 overfilling 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. 30-10-2018 JAMIA HAMDARD (SPER) 17

18. Sample shape It is recommended that the sample is as thin as possible and covers as much of the pan bottom as possible . Samples in the form of cakes (as in case of polymers) must preferably be cut rather than crushed to obtain a thin sample. Crushing the sample , whether in crystalline form or a polymer, induces a stress, which can in turn affect the results . In most case lid should always be used in order to more uniformly heat the sample and to keep the sample in contact with the bottom of the pan. 30-10-2018 JAMIA HAMDARD (SPER) 18

19. Sample Pans Lightest, flattest pans are known to have the least effect on the results obtained from a DSC. Crimped pans on the other hand provide the highest sensitivity and resolution. Hermetic pans are used where the sample is expected to have some volatile content. These pans prevent evaporation. Two main reasons for the use of these pans are – The Tg of a polymer or amorphous material shifts with volatile content. Evaporation peaks look just like melting endotherm. 30-10-2018 JAMIA HAMDARD (SPER) 19

20. Sample Weight Though 5 to 10 mg is considered to be an appropriate sample weight for a DSC test, selection of the optimum weight is dependent on a number of factors: the sample and the change in heat flow due to the transition of interest should be in the range of 01 – 10 mW. For polymer Tg or melting sample the mass should be >>10mg . Polymer composites or blends the sample mass is > 10mg. The accuracy of the analytical balance used to measure the sample weight should be accurate to ±1%. 30-10-2018 JAMIA HAMDARD (SPER) 20

21. Experimental Conditions Start temperature Generally, the baseline should have 2 minutes to completely stabilize prior to the transition of interest. Therefore, at 10 o C/min heating rate the run should start at least 20 o C below the transition onset temperature. End temperature Allowing a 2-min baseline after the transition of interest is considered appropriate in order to correctly select integration or analysis limits. Care should be taken not to decompose samples in the DSC; it not only affects the baseline performance but the cell life. 30-10-2018 JAMIA HAMDARD (SPER) 21

22. Experimental Conditions Reference pan A reference pan of the same type used to prepare the sample should be used at all times. A material in the reference pan that has a transition over the temperature range of interest should never be used. Heating rate Heating the samples at low heating rates increases resolution by providing more time at any temperature. Transitions due to kinetic processes (crystallization) are shifted to lower temperature at highest cooling rates or higher temperatures at high heating rates. 30-10-2018 JAMIA HAMDARD (SPER) 22

23. DSC Calibration Calibration of DSC is done using Indium metal . Calibrating an instrument with a metal when pharmaceuticals are to be studied appears to be not appropriate. To overcome this, an effort has been made to calibrate DSC with pharmaceuticals. The true m.p . of indium metal is 156.7 o C and the observed in calibration is 157.4 o C. It is 0.7 o C high and the instrument values must be adjusted down to accommodate the true melting temperature. 30-10-2018 JAMIA HAMDARD (SPER) 23

24. Sources of errors Calibration Contamination Sample preparation Residual solvents and moisture Thermal lag- heating/cooling rates Processing errors 30-10-2018 JAMIA HAMDARD (SPER) 24

25. Advantages and disadvantages of DSC Advantages Widespread study of thermal properties on an extensive range of sample types. Increased sensitivity for detection of weak transitions Small sampling requirements – a fraction of mg can be used. Disadvantages Usually limited to small sample sizes. Accuracy : transitions can be shifted by as much as 40 o C. Thermogram are often complex and difficult to interpret fully. Confusion can arise unless care is exercised in the interpretation of the thermograms. 30-10-2018 JAMIA HAMDARD (SPER) 25

26. Pharmaceutical applications of DSC Quantitative and Qualitative analysis. Characterization – melting point, heat of fusion, specific heat capacity, etc. Enhanced analysis of polymorphism Detection of low level amorphous content Detection of low energy transitions Stability tests 30-10-2018 JAMIA HAMDARD (SPER) 26

27. DIFFERENTIAL THERMAL ANALYSIS (DTA) 30-10-2018 JAMIA HAMDARD (SPER) 27

28. Differential Thermal Analysis Principle : Monitoring of the temperature difference between a sample and an inert reference as the heat is applied to the system. Endothermic and Exothermic changes in the sample lead to characteristic deviations in temperature, which can be used for qualitative and quantitative analyses. 30-10-2018 JAMIA HAMDARD (SPER) 28

29. Instrumentation Apparatus for DTA consists of: Sample and reference holder A furnace A detector An amplifier A recorder 30-10-2018 JAMIA HAMDARD (SPER) 29

30. Schematic representation of DTA curve . 30-10-2018 JAMIA HAMDARD (SPER) 30

31. Factors affecting result in DTA Sample weight Heating rate Particle size Atmospheric condition 30-10-2018 JAMIA HAMDARD (SPER) 31

32. Advantage and Disadvantage ADVANTAGES Can be operated even at very high temperature. High sensitivity. Accuracy. DISADVANTAGE Reaction or transition estimation is only 20% to 50% in DTA. Uncertainty in heat of fusion. 30-10-2018 JAMIA HAMDARD (SPER) 32

33. Applications of DTA Qualitative and Quantitative estimation of minerals. Analysis of biological material (e.g., assay and thermal stability testing of tetanus toxoid ). Also used for the thermal stability studies of inorganic compounds and complexes (e.g., zeolites ). To determine melting point, boiling point and decomposition temperature of organic compounds. Widely used for the quality control of a large number of substances like cement, glass, soil etc. 30-10-2018 JAMIA HAMDARD (SPER) 33

34. THERMOGRAVIMETRIC ANALYSIS (TGA) 30-10-2018 JAMIA HAMDARD (SPER) 34

35. Thermogravimetric Analysis (TGA) Principle : TGA measures the amount and the rate of change in weight of a sample with respect to temperature (or time). Instrument : The instrument used for thermogravimetry is “ thermobalance ”, and the data recorded is in the form of curve known as “ thermogram ” or “ TG curve ”. 30-10-2018 JAMIA HAMDARD (SPER) 35

36. Instrumentation Basically TGA consists of four major parts – Thermocouple Furnace Auto sampler Microgram balance 30-10-2018 JAMIA HAMDARD (SPER) 36

37. Instrumentation 30-10-2018 JAMIA HAMDARD (SPER) 37

38. Instrumentation The balance is used to record the weight . Its sensitivity is usually of order of 1microgram. The furnace can rise the temperature as high as 1000 o C which is made of quartz. The thermocouple sits right above the sample and it indicates the temperature . The thermocouple should not be in touch with the sample which is in the pan. The auto sampler helps to load the sample on to the microbalance. 30-10-2018 JAMIA HAMDARD (SPER) 38

39. Factors affecting TG curve The major factors affecting the recorded mass (m) and temperature (T) in thermogravimetry are - Condensation and reaction (m) Electrostatic effects (m) Heating rate(T) Gas flow (T) Sample holder (T) Sample size and packing (T) Fortunately, most of the factors can be controlled or the data corrected for their influence. 30-10-2018 JAMIA HAMDARD (SPER) 39

40. TGA curve of Calcium Oxalate (CaC 2 O 4 ) 30-10-2018 JAMIA HAMDARD (SPER) 40

41. Applications of TGA The water content of a sample can be analysed by TG. It can also differentiate between the adsorbed water and constitutional water. In proximate analysis of coal and other similar fuels. To measure the oxygen content in the superconductors. Oxidative stability . Determination of rancidity of edible oils. 30-10-2018 JAMIA HAMDARD (SPER) 41

42. REFERENCES Analytical Chemistry (A Modern Approach to Analytical Science) - by M. Mermet, M. Otto, M. Widmer, 2 nd edition, WILEY-VCH Verleg Gmbh & Co. KGaA, page no. 373-388. Principles and Practice of Analytical Chemistry - by F.W. Fifield & D. Kealey., 5 th edition (year-2000)., Blackwell Publishing., (page no. 477-493). Instrumental Methods of Analysis - by Hobart H. Willard, Dynne L. Merritt, Jr., John A. Dean, & Frank A. Settle, Jr., 7 th edition (year-1988), Wadsworth publication, page no. 761-777. Thermal Analysis Techniques – K.H. Tan (University of Georgia, Athens, Georgia), B.F. Hajek (Auburn University, Auburn, Alabana ), I. Barshad (University of California, Berkeley, California) (Abstract., Published on-1986)., page no. 151. https://link.springer.com/article/10.1007/s40828-015-0008-y 30-10-2018 JAMIA HAMDARD (SPER) 42

43. THANKING YOU 30-10-2018 JAMIA HAMDARD (SPER) 43