Thermal techniques- DSC- Durgashree Diwakar

The techniques in which some physical parameters of the systems are determined and /or recorded as a function of temperature.
DSC is a thermal technique in which differences in heat flow into a substance and a reference are measured as a function of sample temperature while the two are subjected to a controlled temperature program.

1. THERMAL TECHNIQUES -DSC BY- DURGASHREE.M.D MODERN PHARMACEUTICAL ANALYTICAL TECHNIQUES M.PHARM, DEPARTMENT OF PHARMACOGNOSY KLE COLLEGE OF PHARMACY BENGALURU 1

2. CONTENTS Introduction to Thermal Techniques DSC Principle Thermal transition Instrumentation Modulated DSC Hyper DSC Experimental Parameters Advantage and Disadvantages Applications 2

3. INTRODUCTION When a matter is heated, it undergoes certain Physical and Chemical changes. These changes take place over a wide range of temperatures. Physical changes: M.P, B.P, etc. Chemical changes: Decomposition, reactions, etc. So, these changes will become a characteristic of the material, which is under examination. 3

4. Cont. By measuring the temperature at which these types of reactions occur, one can characterize the compound present in the material. Majorly inorganic compounds are characterized. So, Physical and Chemical changes that take place when an unknown sample is heated provide us with information that helps us to identify the material. [1] 4

5. Definition of Thermal Techniques It defines as the techniques in which some physical parameters of the systems are determined and /or recorded as a function of temperature. [1] OR A group of techniques in which a physical property of a substance and /or its reaction product is measured as a function of temperature whilst the substance is subjected to a controlled temperature program. [2] 5

6. Types of Thermal Techniques 6

7. DSC- Differential Scanning Calorimetry DSC is a thermal technique in which differences in heat flow into a substance and a reference are measured as a function of sample temperature while the two are subjected to a controlled temperature program. [2] This technique is used to study what happens to polymer/sample upon heating. [3] 7

8. Principle The sample and references are maintained at the same temperature, even during a thermal event. The energy required to maintain a zero temperature difference between the sample and reference is measured. During the thermal event in the sample, the system will transfer heat to or fro from the sample pan to maintain the same temperature in the reference and sample pans. [3] 8

9. Thermal Transition The molecule has transitioned from one phase to another phase because of the addition of thermal energy. This is called Thermal Phase Transition. Like, At the melting point, molecule or material changes visibly from crystal to liquid. At the boiling point from liquid to vapor. The polymer can also exist in different phases. 9

10. Cont. When we drop a water hose in liquid nitrogen, it gets very brittle, if we drop this on a concrete floor it breaks like a glass tube. This phase in the rubber that exists is called the ‘Glassy state’. If we increase the temperature (Room temp) of the water hose or rubber hose, it becomes flexible. This state is called the ‘rubbery/viscoelastic state’. 10

11. Cont. The temperature at which the glassy state becomes a rubbery state is called Glass Transition Temperature ( Tg ). Further, if we increase the temperature, it starts to melt. This is the Melt phase. The temperature at which a rubbery state becomes a melt state is called Melt temperature(Tm). So this DSC is used to study the Thermal Transition of a polymer/sample. 11

12. Instrumentation There are two pans, in the sample pan polymer is added, while the other, reference pan is left empty. Each pan sits on top of heaters which are controlled by a computer. The computers heat the two pans at a specific rate, usually 10 degrees Celsius/min. The computer makes sure that the heating rate stays the same throughout the experiment 12

13. Cont. Two types of methods are used to obtain DSC data. Power compensate DSC: In this, sample and reference material are heated by separate heaters in such a way that their temp is kept equal while these temperatures are increased linearly. Heat flux DSC: In this, the difference in heat flow into sample and reference is measured as the sample temperature increases or decreased linearly. 13

14. Power Compensate DSC It has two independent furnaces, one for heating the sample and the other for heating the reference. The furnaces are embedded in the large temperature-controlled heat sink. Above the furnace, the sample and reference holders (Pans), which have platinum resistance thermometers embeded in them to monitor temperature of two materials continuously. 14

15. Cont. Two circuits are employed for obtaining differential thermograms with the instrument. One for average temperature control and one for differential temperature control. In average temperature control circuit- a program provides an electrical signal that is proportional to the desired average temperature of the sample and reference holders as a function of time. In differential temperature circuit- Sample and reference signals from the platinum resistance sensors are fed into differentials amplifier through a comparator circuit that determines which is greater. 15

16. Heat Flux DSC Heat flows into both the sample and reference material via electrically heated constantan thermoelectric disk. Small aluminum sample and reference pans sit on raised platforms formed on the constantan disk. Heat is transferred through the disk and up into the sample and reference pans. 16

17. Cont. The differential heat flow to the sample and reference is monitored by chromel /constantan area thermocouples formed by the junction between the constantan platform and chromel disk attached to the underside of the platforms. It can be shown that the differential heat flow into the two pans are directly proportional to the difference in the output of the two thermocouple junction. The sample temp is determined by means of the chromel junction under the sample disk. [2] 17

18. Modulated DSC Modulated DSC uses the same heating and cell arrangement as the heat flux DSC method. It is a new technique introduced in 1993. The main advantage of this is the separation of overlapping events in the DSC scans. In Modulated DSC the normally linear heating ramp is overlaid with the sinusoidal function defined by a frequency and amplitude to produce a sine wave shape temperature versus time function. 18

19. Cont. Using Fourier mathematics, the DSC signal is split into two components: Reversible event No reversible events This modulated DSC is an extension of conventional DSC. Its applicability is recognized for precise determination of the glass transition and for the study of the energy of relaxation. 19

20. Hyper DSC The high resolution of PC-DSC or a new type of power compensating DSC provides the best results for an analysis of melting and crystallization of metals or detection of glass transition temperature ( Tg ) in medication. This technique is especially proper for the pharmaceutics industry for testing medicaments at different temperatures where fast heating rates are necessary to avoid other unwanted reactions. [5] 20

21. Experimental Parameters- 1. Sample preparation Accurately weigh samples (~3-20mg) Small samples pans (0.1ml) of inert or treated metals ( Al, Pt, Ni, etc.) Several pan configurations, e.g., open, pinhole, or hermetically sealed (airtight) pans. The same material and configuration should be used for the sample and the reference. 21

22. 1. Sample preparation The 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. 22

23. 2. Experimental conditions Analytical balance : The analytical balance is used to weigh out the sample. It is often a limiting factor regarding the accuracy of the heat flow signals produced by the DSC. The balance should be checked and calibrated daily against a known traceable reference weight. A 5 digit balance should be considered as a minimum requirement when weighing the sample in the 10 to 20mg range. 6 digit balance for 1 to 10mg range and 7digit balance for sample less than 1mg. 23

24. Cont. b. Purge gas: Most DSC experiments are carried out in an inert atmosphere, usually Nitrogen. Helium which has a higher thermal conductivity can be used if the thermal resistance of the DSC needs to be reduced. A drawback to using helium over nitrogen as a purge gas is that it takes longer for DSC systems to reach equilibrium and stabilize after the cell has opened to air. 24

25. Cont. c. Purge flow: A constant flow of gas through DSC ensures that any volatile products evolved during the DSC experiment are swept away from the measuring sensor. A change in flow can have several effects. First, it may change the temperature and enthalpy calibration. Second, in case evolved volatile substances from the sample when it’s heated, the DSC peak shape will be affected by the speed at which the volatile substance is removed. This can be controlled by using calibrated mass flow controller. 25

26. 3. Calibration a. Temperature calibration : In the DSC experiment where the sample is heated, the sample and its surroundings are not in thermal equilibrium. The sample temp will be slightly lower than the furnace temperature. Temp calibration requires that traceable standards, with known transitions temp, run in the same conditions as those to be used when running samples. It is common to see an operator calibrate with material like indium, lead, or tin, then analyzed the sample with transition in the ambient to 100 degrees C temperature range. 26

27. Cont. b. Enthalpy calibration : Few materials exist that accurately know enthalpies and that are also available with traceable certifications. The material can be used, in a single experiment, to calibrate the DSC for both abscissa and ordinate. The assumption is that a single enthalpy calibration is acceptable for the entire temperature scale. 27

28. 4. Heating rates Several points can be observed as the heating rate increased: a. The baseline curves are increasingly offset. b. The height magnitude and width of the melting peak increase. c. The melting transition is observed at higher temperatures. As the heating rate increases, the width of the melting transition increases, so resolution is decreased. The peak height increases, so the detection limit increases. 28

29. 5. Cooling rates Cooling is often an under-appreciated property of DSC. In controlled cooling, a specific temperature change per minute is specified as a rate between 0.1degrees C/min to 500 degrees C/min and should be maintained throughout the experiment. On ballistic cooling where the sample is cooled as fast as possible. The cooling rate is 400 degrees C/min. For improving cooling times, subambient temp tests, various cooling options such as forced air, intercooler or liquid nitrogen cooling systems are available. 29

30. 6. Resolution One of the most important performance characteristics of the DSC instrument is its Resolution. Enhance resolution can be obtained using helium rather than nitrogen, air, or oxygen purge, due to the significantly higher thermal conductivity of helium. Lower sample masses can provide over larger masses. A slow heating rate will yield significantly better resolution than faster heating rates. 30

31. 7. Sources of errors a. An environmental error: The DSC technique is more sensitive to the gaseous environment around the sample. In DSC studies, two types of gaseous atmosphere are used: 1. A static atmosphere 2. A dynamic gaseous atmosphere A static atmosphere is difficult to reproduce because the atmosphere surrounding the sample is changing in concentration, chemically due to evolved gases and physically due to convection currents. A dynamic atmosphere where the gases are swept past the sample in a controlled way is reliable and reproducible. 31

32. Cont. b. Instrumental error: The geometry and the material used in the fabrication of the sample holder affect the resolution, shape, and size of the DSC peaks. In furnace heating rate increases, the resolution decreases and experiment time decreases. If the winding used in the furnace is not uniform, the baseline is changed. The heating rate has s great influence on the DSC curve. 32

33. Cont. c. Sample characteristics : The particle alters the peak area. This decreases with increasing particle size. Particle size also influences the peak temperature. Generally, with an increase in particle size, the peak temp is shifted to higher values. The shape of the sample has little effect on the quantitative aspects and has more effect on qualitative aspects of DSC. About 0.5 to 10mg is usually sufficient. Smaller samples enable faster scanning, give better shape peaks with good resolution and provide better contact with the gaseous environment. 33

34. Advantages Instruments can be used at very high temperatures. Instruments are highly sensitive. Characteristic transition or reaction temperature can be determined. The high resolution is obtained. Stability of the materials. A small amount of material is needed . 34

35. Disadvantages Interpretation of results is often difficult. Quantitative analysis of the individual processes is impossible. Cannot optimize both sensitivity and resolution in a single experiment. Very sensitive to any changes. 35

36. Applications Identification of substance: The DSC curve for two substances is not identical. Therefore serves as fingerprints for various substances. Identification of product: The products are identified by their specific DSC curves. Quantitative analysis: the areas of DSC peak are 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 v/s weight. 36

37. Application Quality control: DSC technique has been widely used for the quality control of several substances like glass, catalysts, resins, etc. Protein stability: It measures the extent to which the stability and thermodynamics are affected by the simple effects associated with variation in protonation of macromolecules. Antibody domain studies: stability of the antibodies are analyzed during the development process. [6] 37

38. References Gurdeep R. Chatwal, Sham K. Anand – Instrumental Method of Chemical Analysis. Skoog. Holler. Nieman- Principle of Instrumental Analysis. DSC- Khalid Hussain. ( https://www.slideshare.net/hussain_761/differential-scanning-calorimetry ) Thermal Transition in Polymer- Suhas Kulkarni. ( https://knowledge.ulprospector.com/1203/pe-thermal-transitions/ ) Thermal techniques and DSC. ( https://www.slideshare.net/AmrutaBalekundri/thermal-technique-and-differential-scanning-calorimetry ) Experimental parameters- DSC – Shikha Popali . 38

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