THERMAL ANALYICAL TECHNIQUES TGA-4238.pptx

Themal analytical techniques

1. Thermal Analysis CHEM-4238 1 Thermal analysis is a branch of materials science where the properties of materials are studied as they change with temperature. Several methods are commonly used – these are distinguished from one another by the property which is measured. DR SHAHZAD SHARIF

2. 2 Thermogravimetric analysis (TGA): mass Differential thermal analysis (DTA): temperature difference Differential scanning calorimetry (DSC): heat difference Pressurized TGA (PTGA): mass changes as function of pressure. Thermo mechanical analysis (TMA): deformations and dimension Evolved gas analysis (EGA): gaseous decomposition products Often different properties may be measured at the same time: TGA-DTA, TGA-EGA, TGA-DSC Thermal analysis ... Includes several different methods. These are distinguished from one another by the property which is measured

3. Common Thermal Analysis Methods and the Properties Measured 3

4. Introduction Thermal analysis is defined as “series of techniques for measuring the temperature dependency of a physical/chemical property of a certain substance while varying the temperature of the substance according to a specific program.” The substance referred to here includes reaction products. Physical/chemical properties include mass, temperature, enthalpy, dimension, dynamic characteristics, and others, and depending on the physical properties to be measured, the techniques of thermal analysis. 4

5. Introduction Conventionally thermal analysis has been mainly employed in measurements for research and development, but in recent times it is used in many practical applications, as the testing standards on the basis of thermal analysis have been established, for example, in quality control in the production field, process control, and material acceptance inspection. It is also applied in wide fields, including polymer, glass, ceramics, metal, explosives, semiconductors, medicines, and foods. Solid state chemistry uses thermal analysis for studying reactions in the solid state, thermal degradation reactions, phase transitions and phase diagrams. 5

6. TGA (Thermogravimetric analysis) Measures changes in weight in relation to changes in temperature. The measured weight loss curve gives information on: changes in sample composition thermal stability kinetic parameters for chemical reactions in the sample A derivative weight loss curve can be used to tell the point at which weight loss is most apparent 6 The technique can characterize materials that exhibit weight loss or gain due to decomposition, oxidation, or dehydration

7. TGA; Phenomena causing mass changes 7 Thermogram

8. TGA: Applications Characterization of Thermal stability Material purity Composition of multi-component systems Determination of humidity Examination of Corrosion studies (e.g. oxidation or reactions with reactive gases) Gasification processes lifetime of a product Kinetic processes 8

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16. Interpretation of TG and DTG curves The sample undergoes no decomposition with loss of volatile products over the temperature range shown but solid phase transformation, melting ,etc can not be detected by TG , The rapid initial mass loss is characteristic of desorption or drying. If it is true, then re-run the sample should result in type ( i ) curves , Single stage decomposition , Multi-stage decomposition with relatively stable intermediates : provide information on the temperature limit of stability of reactants and intermediate products and also stoichiometry , Multi-stage decomposition with no stable intermediate product. However heating-rate effect must be considered. At low heating rate, type (v) resemble type (iv). At high heating rate, type (iv) and (v) resemble type (iii) and lose all the details , Gain in mass due to reaction with atmosphere, e.g. oxidation of metals , Oxidation product decompose again at higher temperature; this is not often encountered. 16

17. Perkin Elmer Thermal Analysis Systems http://www.perkin-elmer.com/thermal/index.html TA Instruments http://www.tainst.com/ Mettler Toledo Thermal Analysis Systems http://www.mt.com/ Rheometric Scientific http://www.rheosci.com/ Haake http://polysort.com/haake/ NETZSCH Instruments http://www.netzsch.com/ta/ SETARAM Instruments http://setaram.com/ Instrument Specialists, Inc. http://www.instrument-specialists.com/ 17 Thermal Analysis Instrument Manufacturers

18. 18 A second approach to gravimetry is to thermally or chemically decompose a solid sample. The volatile products of the decomposition reaction may be trapped and weighed to provide quantitative information. Alternatively, the residue remaining when decomposition is complete may be weighed. In thermogravimetry , which is one form of volatilization gravimetry, the sample’s mass is continuously monitored while the applied temperature is slowly increased TGA Thermogram A graph showing change in mass as a function of applied temperature. The change in mass at each step in a thermogram can be used to identify both the volatilized species and the solid residue.

19. EXAMPLE The thermogram in the above Fig. shows the change in mass for a sample of calcium oxalate monohydrate, CaC2O4 × H2O. The original sample weighed 24.60 mg and was heated from room temperature to 1000 °C at a rate of 5 °C min. The following changes in mass and corresponding temperature ranges were observed: Loss of 3.03 mg from 100–250 °C Loss of 4.72 mg from 400–500 °C Loss of 7.41 mg from 700–850 °C Determine the identities of the volatilization products and the solid residue at each step of the thermal decomposition. 19

20. 20 The loss of 3.03 mg from 100–250 °C corresponds to a 12.32% decrease in the original sample’s mass. In terms of CaC2O4 × H2O, this corresponds to a loss of 18.00 g/mol. 0.1232 ´ 146.11 g/mol = 18.00 g/mol The product’s molar mass, coupled with the temperature range, suggests that this represents the loss of H2O. The residue is CaC2O4. The loss of 4.72 mg from 400–500 °C represents a 19.19% decrease in the original mass of 24.60 g, or a loss of 0.1919 ´ 146.11 g/mol = 28.04 g/mol This loss is consistent with CO as the volatile product, leaving a residue of CaCO3. Finally, the loss of 7.41 mg from 700–850 °C is a 30.12% decrease in the original mass of 24.60 g. This is equivalent to a loss of 0.3012 ´ 146.11 g/mol = 44.01 g/mol suggesting the loss of CO2. The final residue is CaO .

21. 21 Once the products of thermal decomposition have been determined, an analytical procedure can be developed. For example, the thermogram in above Figure. shows that a precipitate of CaC2O4 × H2O must be heated at temperatures above 250 °C, but below 400 °C if it is to be isolated as CaC2O4. Alternatively, by heating the sample to 1000 °C, the precipitate can be isolated as CaO . Knowing the identity of the volatilization products also makes it possible to design an analytical method in which one or more of the gases are trapped. Thus, a sample of CaC2O4 × H2O could be analyzed by heating to 1000 °C and passing the volatilized gases through a trap that selectively retains H2O, CO, or CO2. CONCLUSION

22. 22 Schematic principle of TGA measurement A technique measuring the variation in mass of a sample undergoing temperature scanning in a controlled atmosphere Thermobalance allows for monitoring sample weight as a function of temperature The sample hangs from the balance inside the furnace and the balance is thermally isolated from the furnace

23. 23 TEMPERATURE PROGRAMMER BALANCE CONTROLLER POWER FURNACE TEMP. SAMPLE TEMP. WEIGHT GAS IN

24. 24 balance/furnace configurations

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26. 26 Desolvation – adsorbed and bound solvents, stoichiometry of hydrates and solvates Decomposition – chemical and thermal stability Compatibility – interactions between components TA INSTRUMENTS: TGA/DSC

27. C 8 H 10 CeNO 10, 420.29 27 DR SHAHZAD SHARIF

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29. 29 At the first stage water is released, corresponding to the weight loss of about 17.4% (calculated value 17.1% for three coordinated waters and one non-coordinated water molecule) between 65-240°C. The second weight loss of 41.5% up to 790°C results from the successive release of pyridine tricarboxylate anion ( calcd . 41.9%). The overall weight loss of 58.9% is in a good agreement to the calculated value (59%), assuming 41.1% CeO 2 as the final product ( calcd . 40.9%). The residual mass also indicates the conversion of oxidation state from Ce (III) to Ce (IV).

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33. 33 C 14 H 19 LaN 2 O 14 578.22

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35. 35 At the first stage water is released, corresponding to the weight loss of about 17.9% (calculated value 18.7 % for 2 coordinated and 4 non coordinated water molecules) between 90-160°C. At 280°C the polymer begins to decompose as the second weight loss of 49.8% up to 810 results from the successive release of pydc (calculated value 48.9%). The residual mass of 28.7 % corresponds to the formation of lanthanum oxide.

36. 36 TGA curve of two different cured epoxy resins

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40. 40 Differential Scanning Calorimetry (DSC) Most popular thermal technique DSC measures the heat absorbed or liberated during the various transitions in the sample due to temperature treatment Differential: sample relative to reference Scanning: temperature is ramped Calorimeter: measures heat DSC measurements are both qualitative and quantitative and provide information about physical and chemical changes involving: Endothermic processes – sample absorbs energy Exothermic processes – sample releases energy Changes in heat capacity

41. 41 The energy changes enable the user to find and measure the transitions that occur in the sample quantitatively, and to note the temperature where they occur, and so to characterize a material for melting processes, measurement of glass transitions and a range of more complex transitions. The main property that is measured by DSC is heat flow, the flow of energy into or out of the sample as a function of temperature or time, and usually shown in units of mW on the y-axis. Since a mW is a mJ /s this is literally the flow of energy in unit time. The actual value of heat flow measured depends upon the effect of the reference and is not absolute. DSC measures differences in the amount of heat required to increase the temperature of a sample and a reference as a function of temperature

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43. 43 Two separat heating circuits: The average-heating controller The temperatures of the sample (Ts) and reference ( Tr ) are measured and averaged and the heat output is automatically adjusted to increase the average temperature of the sample and reference in a linear rate Differential-heating circuit Monitor the difference in Ts and Tr , and automatically adjust the power to either the reference or sample chambers to keep the temperatures equal

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45. 6 DSC Thermogram Temperature Heat Flow - > exothermic Glass Transition Crystallisation Melting Cross - Linking (Cure) Oxidation 45

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47. 47 Melting points – crystalline materials Desolvation – adsorbed and bound solvents Glass transitions – amorphous materials Heats of transitions – melting, crystallisation Purity determination – contamination, crystalline/amorphous phase quantification Polymorphic transitions – polymorphs and pseudopolymorphs Processing conditions – environmental factors Compatibility – interactions between components Decomposition kinetics – chemical and thermal stability

48. 48 Encapsulation To prevent contamination of the analyser , and to make sure that the sample is contained and in good thermal contact with the furnace unexpected peaks and bumps in the DSC trace with no real cause or meaning range of sample pans for different purposes Temperature range Aluminum must not be used above 600◦C Gold (mp 1063◦C), platinum or alumina can be used at higher temperatures

49. 49 Pressure build-up and pan deformation hermetically sealed pan sample leakage and bursting very high temperature or pressure, capsules which hold internal pressures up to 150 bar should be used Reactions with the pan choose a pan type which is inert Pan cleanliness trace of machine oils used in pan manufacture

50. 50 Liquid samples placed in sealed pans of a type that can withstand any internal pressure build-up Sample contact Samples need to be in good thermal contact with the pan Low-density samples provide poor heat transfer so should be compressed Spillage Remove particles outside the pan

51. 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. 51

52. 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. 52

53. 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 to be analyzed must be representative of the total sample and the change in heat flow due to the transition of interest should be in the range of 0.1 - 10mW A recommendation for metal or chemical melting sample is < 5mg. 53 The amount of sample used will vary according to the sample and application

54. Sample Weight For polymer glass transition 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%. 54 For most work a five-figure balance is needed, and six figures (capable of measuring to the microgram level) for more accurate heats of fusion

55. Experimental Conditions Start Temperature End Temperature Reference Pan Heating Rate 55

56. Start Temperature Generally, the baseline should have 2 minutes to completely stabilize prior to the transition of interest. Therefore, at 10°C/min heating rate the run should start at least 20°C below the transition onset temperature. 56 The starting temperature should be well below the beginning of the first transition With ambient DSC systems the starting temperature is often around 30◦C.

57. End Temperature Allowing a 2-minute 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. 57 It is good practice to establish the decomposition temperature first using a TGA analyser if available The upper temperature should be below the decomposition temperature

58. 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 in the temperature range of interest should never be used. 58

59. 59 Purge gas The most common purge gas is nitrogen Air and oxygen are sometimes used for OIT (oxidative induction time) Helium is used for work at very low temperatures Argon have been used and this can be helpful when operating at higher temperatures, typically above 600◦C Air, nitrogen and oxygen have similar thermal conductivities and instrument calibration is unaffected if they are switched The use of helium or argon requires separate calibrations to be performed copper or steel gas lines pressure leakage could be checked by soap bubble flow

60. 60 Differential scanning calorimetry (DSC) monitors heat effects associated with phase transitions and chemical reactions as a function of temperature . In a DSC the difference in heat flow to the sample and a reference at the same temperature, is recorded as a function of temperature. The reference is an inert material such as alumina, or just an empty aluminum pan. The temperature of both the sample and reference are increased at a constant rate. The heat flow difference can be either positive or negative . dH / dt is the heat flow, in an endothermic process, such as most common phase transitions, heat is absorbed and, therefore, heat flow to the sample is higher than that to the reference . Hence DdH / dt is positive.

61. 61 The basic principle underlying this technique is that when the sample undergoes a physical transformation such as phase transitions, more or less heat will need to flow to it than the reference to maintain both at the same temperature. Whether less or more heat must flow to the sample depends on whether the process is exothermic or endothermic. For example, when a solid sample melts to a liquid it will require more heat flowing to the sample to increase its temperature at the same rate as the reference. This is due to the absorption of heat by the sample as it undergoes the endothermic phase transition from solid to liquid. Likewise, as the sample undergoes exothermic processes (such as crystallization) less heat is required to raise the sample temperature. By observing the difference in heat flow between the sample and reference , differential scanning calorimeters are able to measure the amount of heat absorbed or released during such transitions.

62. 62 Ice at colder temperature can have different crystal structures and undergo many solid-solid phase transitions, and in each of these phases, the ice has different properties ranging from brittleness to conductivity. By understanding the technique and instrumentation of DSC, it is possible to understand what the materials go through different changes during energy gain or loss.

63. 63 It's pretty simple, really. There are two pans. In one pan, the sample pan, you put your polymer sample. The other one is the reference pan. You may leave it empty . Each pan sits on top of a heater. When you tell the computer to turn on the heaters. So the computer turns on the heaters, and tells it to heat the two pans at a specific rate , usually something like 10 o C per minute . The computer makes absolutely sure that the heating the rate stays exactly the same throughout the experiment. But more importantly, it makes sure that the two separate pans, with their two separate heaters, heat at the same rate as each other . The sample means there is extra material in the sample pan. Having extra material means that it will take more heat to keeps the temperature of the sample pan increasing at the same rate as the reference pan.

64. 64 So the heater underneath the sample pan has to work harder than the heater underneath the reference pan. It has to put out more heat. By measuring just how much more heat it has to put out is what we measure in a DSC experiment . Specifically, we can make a plot as the temperature increases on the x-axis. On the y-axis we plot difference in heat output of the two heaters at a given temperature. When we start heating our two pans, the computer will plot the difference in heat output of the two heaters against temperature. That is to say, we're plotting the heat absorbed by the polymer against temperature. The plot at first will look something like as shown below.

65. 65 The heat flow is going to be shown in units of heat, q supplied per unit time, t. The heating rate is temperature increase T per unit time ,

66. 66 Consider, for example, two pots, one with water and one empty, and both pots start out at the same initial temperature and are then placed on stoves. If each pot is heated at the same rate (both stove settings are placed on low, for example) the pot with the water in it will heat up slower, that is the rate of temperature change will be smaller than the pot with nothing. This is because heat capacity is different for water than it is for air. Since the pot with the water in it will heat up slower than the empty pot, the computer will have to supply a higher heat flow to the pot containing water in order to force the pots to heat at the same rate.

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68. 68 Besides temperature, you can also look at phase transitions when performing calorimetric experiments. A liquid sample can be made gaseous by adding energy. Adding energy increases the temperature of the sample, until it begins to boil. Then, the temperature remains constant. When the sample is evaporated completely, its temperature increases again. The opposite is also possible: by removing energy, its temperature decreases and the sample starts freezing. In a phase transition the chemical composition of the sample doesn't change. Only its phase changes by adding or removing energy. Phase changes are possible between all the three phases and as well as between two solid phases. The temperature at which the phase transition occurs, is called the transition temperature Ttrs .

69. 69 Differential scanning calorimetry (DSC) is an experimental technique for measuring the energy necessary to establish a nearly-zero temperature difference between a test substance S (and/or its reaction products) and an inert reference material R, while the two samples are subjected to an identical (heating, cooling or constant) temperature programme. Two types of DSC systems are commonly in use. 1- Power-compensation DSC (developed by perkinelmer ) : The specimen (TS) and reference (TR) temperatures are controlled independently using separate (identical) ovens each with a heater coil and a thermocouple. The temperature difference between the sample and reference is maintained to zero, even during a thermal event in the sample by varying the power input to the two furnaces. This energy is then a measure of the enthalpy or heat capacity changes in the test specimen S (relative to the reference R).

70. 70 Schematic of a DSC. You choose the linear temperature scan rate. The triangles are amplifiers that determine the difference in the two input signals. The sample heater power is adjusted to keep the sample and reference at the same temperature during the scan.

71. 71 A technique in which the temperature difference between a test specimen and a reference specimen occurring through subjecting both specimens to the same controlled temperature program is compensated by appropriately adjusting the difference of heating power to the test and reference specimen . The differential heating power is recorded against temperature or time.

72. 72 2- (developed by TA instruments) The main assembly of a typical heat-flux DSC cell is enclosed in a heating block (for example Ag), which dissipates heat to the specimens (S and R) via a constantan ( copper 55 per cent and nickel 45 per cent) disc attached to the Ag block. The constantan disc has two platforms on which the S (specimen) and R (reference) pans are placed. A chromel  (90 percent nickel and 10 percent chromium) disc and connecting wire are attached to the underside of each platform: the resulting chromel -constantan thermocouples are used to determine the differential temperatures of interest. Alumel ( 95% nickel, 2% manganese, 2% aluminium and 1% silicon) wires are also attached to the chromel discs to provide chromel-alumel junctions which measure the sample and reference temperatures separately. Another thermocouple is embedded in the Ag block and serves as temperature controller for the programmed heating/cooling cycle.

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74. 74 In heat-flux DSC instruments, the difference in energy required to maintain both S and R at the same temperature is a measure of the energy changes in the test specimen S (relative to the inert reference R). The temperature difference DT that develops between S and R is proportional to the heat-flow between the two. In order to detect such small temperature differences, it is essential to ensure that both S and R are exposed to the same temperature programme. The sample and reference are both within the same furnace and are connected by a low-resistance heat-flow path. If any difference in temperature develops, heat flows in proportion to that temperature difference.

75. 75 Top Furnace View Side Furnace View (R = Reference, S = Sample) (Heating Elements In Red)

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77. 77 Melting and recrystallization When you continue heating, eventually the sample will begin to melt. But to keep the temperature of the sample and reference the same, more heat is needed for the sample. In a plot of heat flow against temperature an endothermal peak (increase of heat flow) will become visible. An exothermal peak (decrease of heat flow) will appear when solidification occurs. This means that when sample reach the melting temperature, the sample temperature won't rise until all the crystals have melted. This means that the little heater under the sample pan have to put a lot of heat into the polymer in order to both melt the crystals and keep the temperature rising at the same rate as that of the reference pan.

78. 78 A first order transition is characterized by its baseline and the peak. In such a curve there are a couple of characteristic temperatures: the beginning of melting, the peak temperature and the return to the baseline. And none of these is the same as the melting point. To determine the melting point, one has to extrapolate the baseline and the left tangent of the temperature peak

79. 79 Melting is an endothermic process since the sample absorbs energy in order to melt. A first-order phase transition is characterized as a change in specific volume accompanied by a latent heat. The most common example studied by DSC is melting. The factor that determines the speed of the transition is the rate at which heat can be supplied by the calorimeter. The area under the peak is a measure of the latent heat of the transition. There are various theories as to what causes a material to melt and what is actually happening on the molecular level as it melts. Lindemann (1910) theorized that melting is caused by instability in the crystal lattice structure due to vibrations. As the temperature increases, the vibrational amplitudes increase, finally reaching a critical fraction of the lattice distance that renders the crystal unstable. A material cannot melt unless it is a crystal

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81. 81 2-[(2, 5-dichlorophenyl) sulfonyl ]-2-azaspiro [4.5] decan-3-one (C 15 H 17 Cl 2 NO 3 S) {1-[({[4-( acetylamino ) phenyl] sulfonyl } amino) methyl] cyclohexyl } acetic acid (C 17 H 24 N 2 O 5 S)

82. Melting Process by DSC 82

83. Purity Determination 83

84. 84 Glass transition temperature An amorphous sample that is heated from below to above the glass transition temperature will become more crystalline. This transition takes time, so in a plot of heat flow against temperature (with constant heating rate) the increase of the baseline is spread over a temperature range. For the glass transition temperature the middle of the incline is chosen

85. Thermal Analysis Methods Used in Pharmaceutical Two individual heaters are used with pc-DSC to control the flow of heat to the sample and reference holders. Individual resistance sensors are positioned within each holder and temperature is measured at the base of each. When a phase change takes place in a in thermal analysis and a temperature difference is observed between the sample and reference, energy is removed or supplied until the temperature difference is lower than the threshold. 85

86. DSC- Principle Principle DSC is a thermo-analytical 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. The differences in heat flow occur with the occurrence of two major events: 1) The heat capacity of the sample which increases with temperature (baseline) 2) Transitions that occur in the sample (events superimposed on the heat capacity baseline) 86

87. Principle Of DSC 87 Goa College of Pharmacy, Goa.

88. Heat Flux This consists of a large single furnace which acts as an infinite heat sink to provide or absorb heat from the sample. The advantages generally include a better baseline, sensitivity and sample–atmosphere interaction. The key components are the Sample pan (typically an aluminum pan and lid) which is combined with the Reference pan (always the same material as the Sample pan, aluminum). 88

89. Heat Flux The Dynamic sample chamber is the environment of the sample pan compartment and the purge gas. Nitrogen is the most common gas, but alternate inert gas is helium or argon. When using an oxidative atmosphere air or oxygen are the gases of choice. The heat flux DSC is based on the Change in Temperature ΔT between the sample and reference. 89

90. Heat Flux and DSC 90

91. Heat Flux Type DSC 91

92. Power Compensation Small individual furnaces use different amounts of power to maintain a constant ΔT 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 heaters monitors the difference between the sample and reference. Platinum resistance thermometers track the temperature variations for the sample and reference cells. 92

93. Power Compensation Holes in the compartment lids allow the purge gas to enter and contact the sample and reference. There are physical differences between the heat flux and power compensated thermal analysis, the resulting fusion and crystallization temperatures are the same. The heat of transition is comparable quantitatively. 93

94. Power Compensation DSC Cell Design 94

95. Power Compensated DSC 95

96. Principles of DSC Analysis 96

97. Effect of Heating Rate 97

98. Summary of DSC experimental conditions 98

99. Summary of Pharmaceutically Relevant Information Derived from DSC Analysis 99

100. Typical Features of a DSC Trace 100

101. 101 Melting Negative peak on thermogram Ordered to disordered transition T m , melting temperature Melting happens to crystalline polymers; Glassing happens to amorphous polymers Temperature, K Thermogram dH/dt, mJ/s Melting T m

102. Amorphous Material 102

103. 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 melting temperature of indium metal is 156.7°C and the observed in calibration is 157.4°C. It is 0.7°C high and the instrument values must be adjusted down to accommodate the true melting temperature. 103

104. DSC Calibration curve of indium 104

105. Glass Transition Temperature ( Tg ) The glass transition is due to the presence of amorphous structures in the sample. It is detected by DSC based on a step-change in molecular mobility that results in a step increase in heat capacity and heat flow rate. Amorphous materials flow, they do not melt and hence no DSC melt peak. The physical and reactive properties of amorphous structure are different than crystalline structure. The physical and reactive properties of amorphous structure are significantly different at temperatures above and below Tg . The glass transition temperature, Tg , is a second order pseudo transition. It constitutes a parameter of high interest in the study of amorphous and semi-crystalline drugs since amorphous drugs are more bio available and soluble. 105

106. 106 Glass Transition Step in thermogram Transition from disordered solid to liquid Observed in glassy solids, e.g., polymers T g glass transition temperature Temperature, K Thermogram dH/dt, mJ/s Glass transition T g

107. Crystallization temperature ( Tc ) The Tc of many drugs has been determined in our lab based on a DSC that can program heat and cool. The difference in Tm to determine the Tc is a measure of super cooling, e.g. Vanillin has a 50°C super cooling temperature while indium melts and crystallizes at the same temperature or super cooling is zero °C 107

108. 108 Crystallization Sharp positive peak Disordered to ordered transition Material can crystallize! Observed in glassy solids, e.g., polymers T c crystallization temperature Temperature, K Thermogram dH/dt, mJ/s Crystallization T c

109. Typical TGA and DSC Results for Various Transitions 109

110. Lactose monohydrate 110 DR SHAHZAD SHARIF