Differential thermal analysis and it's pharmaceutical application

DTA

1. DIFFERENTIAL THERMAL ANALYSIS AND IT’S PHARMACEUTICAL APPLICATION Presented By, J .PRAKASH M.Pharm Ist sem Department of pharmaceutical Analysis 1

2. THERMAL ANALYSIS A group of technique in which physical property of substance or its reaction product is measured as function of temperature whilst the substance is subjected to a controlled temperature Physical properties include –mass, temperature, enthalpy, dimension, dynamic characteristics and others for measured techniques of thermal analysis. 2

3. Endothermic reaction is any chemical reaction than absorbs the heat from its surrounding. The absorbed energy provides the activation energy for the reaction to occur. The physical properties include fusion, vaporization, sublimation, absorption, and desorption. Exothermic reaction is a process in which the heat is evolved from the sample, thus causing its temperature to rise. The physical properties include adsorption and crystallization 3

4. METHODS Thermo gravimetric analysis (TG) Differential Thermal Analysis (DTA) Differential Scanning Calorimetry (DSC) 4

5. THERMOGRAVIMETRIC ANALYSIS: The mass of a sample in a controlled atmosphere is recorded continuously as a function of temperature or time as the temperature of sample is increased. A plot of mass percentage as a function of time is called thermogram or thermal decomposition curve. DIFFERENTIAL SCANNING CALORIMETRY (DSC): It is a thermal technique in which difference in heat flow into substance and reference are measured as function of sample temperature while two are subjected to a controlled temperature program. 5

6. DIFFERENTIAL THERMAL ANALYSIS: It is a technique in which the difference in temperature (ΔT) between a substance and reference material is measured as a function of temperature while the substance and reference material are subjected to controlled temperature program. 6

7. Instrumentation Simply this instrument consists of Sample holder comprising thermocouples, samples containers and a ceramic or metallic block Furnace Temperature programmer Recording system 7

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9. A schematic of the furnace compartment of a differential thermal analyzer. A few milligrams of the sample (S) and an inert reference substance (R) are contained in small aluminum dishes located above sample and reference thermocouples in an electrically heated furnace. The reference material is an inert substance such as alumina, silicon carbide, or glass beads 9

10. General Principles 10

11. The glass transition temperature T g is the characteristic temperature at which glassy amorphous polymers become flexible or rubber- like because of the onset of the concerted motion of large segments of the polymer molecules Two maxima and a minimum are observed in the thermogram. The two maxima are the result of exothermic processes in which heat is evolved from the sample, thus causing its temperature to rise The minimum labeled “melting” is the result of an endothermic process in which heat is absorbed by the analyte. Crystal formation is responsible for the first exothermic peak. 11

12. The third peak is exothermic and is encountered only if the heating is performed in the presence of air or oxygen. This peak is the result of the exothermic oxidation of the polymer. The final negative change in Δ T results from the endothermic decomposition of the polymer to produce a variety of products. DTA peaks result from both physical changes and chemical reactions induced by Temperature changes in the sample. 12

13. Applications of DTA DTA is considered a qualitative technique. Although able to measure the temperatures at which various changes occur, DTA is unable to measure the energy associated with each event. DTA is a widely used tool for studying and characterizing polymers. This illustrates the types of physical and chemical changes in polymeric materials that can be studied by differential thermal methods. 13

14. DTA is also widely used in the ceramics and metals industry. The technique is capable of studying high-temperature processes (up to 2400°C for some units) and relatively large sample sizes (hundreds of milligrams). DTA is used to study decomposition temperatures, phase transitions, melting and crystallization points, and thermal stability. An important use of DTA is for the generation of phase diagrams and the study of phase transitions 14

15. A differential thermogram of sulfur, the peak at 113°C corresponds to the solid-phase change The peak at 124°C corresponds to the melting point of the element. Liquid sulfur is known to exist in at least three forms, and the peak at 179°C apparently involves these transitions the peak at 446°C corresponds to the boiling point of sulfur. 15

16. The DTA method also provides a simple and accurate way of determining the melting, boiling, and decomposition points of organic compounds. thermograms for benzoic acid at atmospheric pressure ( A ) and at 13.79 bar ( B ). The lower temperature peak corresponds to the melting point and the second peak to the boiling point of the acid 16

17. Advantages Instruments can be used at very high temperatures. Instruments are highly sensitive. Characteristic transition or reaction temperatures can be accurately determined. Disadvantages Uncertainly of heats of fusion, transition, or reaction estimations is 20-50%   17

18. FACTORS AFFECT RESULTS IN DTA Sample weight Particle size Heating rate Atmospheric conditions Conditions of sample packing into dishes 18

19. Sample weight The amount of sample taken is effect in the DTA curve change in peak size and position, the amount of sample mass must be standardized Particle size The particles size effect in curves reproducibility, the irreproducible curves are solved by using small amount of sample and it must be in uniform particle size Heating rate The change in heating rate produce change in peak size and position, it is corrected by using a low heating rate 19

20. Atmospheric conditions The sample cell is surrounded by the atmospheric air, it effects change in the curve, inert gas allowed to flow to solve this problem. Conditions of sample packing into dishes The packing density effect on the reproducibility of the curves and the sample container effect on change in peak. The conditions of sample packing into dishes are standardized to solve this problem. 20

21. Thermal Analysis Study of Antihypertensive Drug Telmisartan Method: DTA Analysis were made using simultaneous TG-DTA apparatus thermal analyzer (Shimadzu DTG-60H). The experiments were performed between ambient and 1000 °C. The temperature program had a heating rate 10 °C/min. Dry nitrogen at a low rate of 30 ML/min was used as the purge gas. The sample mass was kept in the range of 5 mg. α-Al2O3 was used as the reference material. 21

22. 22 DTA curve of Telmisartan shows an endothermic flattened peak with its maximum at 456.63 °C. The main thermal decomposition reaction is endothermic peaks Exothermic peaks at 569.27 °C and 610.90 °C may be due to the pyrolysis of the compound. the compound has an endothermic reaction which is not accompanied by weight loss, the reaction has its maximum at 265.84 °C. This reaction is endothermic and may be attributed to melting of the compound.

23. CONCLUSION Differential thermal analysis is a method of determining the temperature difference between sample and reference materials, it can give about the phase properties of a material at different temperatures. The information obtained by the DTA have great benefit to industries, hence it’s widespread use. 23

24. REFERENCES Principles of Instrumental Analysis Seventh Edition by skoog , holler and crouch www.slideshare.net Advanced Pharmaceutical Bulletin, Refaat Ahmed Saber, Ali Kamal Attia, Waheed Mohamed Salem 2014, 4(3), 283-287 24

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