T = TS - TR,
DTA
sensors
Pt/Rh atau chromel/alumel thermocouples Satu untuk sampel dan satu untuk reference Dihubungkan dengan pengontrol suhu diferensial
sample pan reference pan
furnace
alumina block berisi sampel dan reference
temperature controller
Mengontrol program suhu dan atmosfer furnace
kelemahan:
Ketidakpastian estimasi panas bagi reaksi, transisi dan fusi sekitar 20-50%
DTA
sample pan
reference pan
sample holder
Al or Pt pans
sensors
T=0
Pt resistance thermocouples separate sensors and heaters for the sample and reference furnace separate blocks for sample and reference cells
temperature controller
differential thermal power is supplied to the heaters to maintain the temperature of the sample and reference at the program value
Sample Preparation
accurately-weigh samples (~3-20 mg) small sample pans (0.1 mL) of inert or treated metals (Al, Pt, Ni, etc.) several pan configurations, e.g., open , pinhole, or hermetically-sealed pans the same material and 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
Al
Pt
alumina
Ni
Cu
quartz
sample holder sample and reference are connected by a low-resistance heat flow path Al or Pt pans placed on constantan disc sensors
constantan chromel/alumel wires
inert gas vacuum
sample pan
reference pan
thermocouples
chromel wafer
chromel-constantan area thermocouples (differential heat flow) chromel-alumel thermocouples (sample temperature) furnace one block for both sample and reference cells temperature controller the temperature difference between the sample and reference is converted to differential thermal power, d q/dt, which is supplied to the heaters to maintain the temperature of the sample and reference at the program value
temperature
TR TRP
thermal resistances of a heat-flux system change with temperature the measured temperature difference is not equal to the difference in temperature between the sample and the reference
Texp TS TR
DSC Calibration
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 amplified DSC signal is automatically varied with temperature to maintain a constant calorimetric sensitivity with temperature
DSC Calibration
temperature 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 (0.52.0 C/min), and similar sample and reference pan weights calibrants high purity accurately known enthalpies thermally stable light stable (h ) nonhygroscopic unreactive (pan, atmosphere) metals In 156.6 C; 28.45 J/g Sn 231.9 C Al 660.4 C inorganics KNO3 128.7 C KClO4 299.4 C organics polystyrene 105 C benzoic acid 122.3 C; 147.3 J/g anthracene 216 C; 161.9 J/g
TGA
File: Y:\Data\TGA\Calcium oxalate\032304.001 Operator: SLT Run Date: 23-Mar-04 14:57 Instrument: 2950 TGA HR V5.4A
120
Weight (%)
temperature calibration based on ferromagnetic transition of Curie point standards (e.g., Ni) larger sample masses, lower temperature gradients, and higher purge rates minimize undesirable buoyancy effects
100
12.15%
80
19.32%
60
29.99%
40
Time (min)
sulphapyridine
thermal stability melting crystallization solid-state transformations desolvation glass transition sublimation decomposition
heat flow heat of fusion heat of transition heat capacity
1.0
0.5
0.0
-0.5
-1.0
-1.5
Form I I Form Form II II Form Variable Form III Hydrate Dihydrate Acetic acid solvate
-2.0
-2.5 0
Exo Up
50
100
150
200
250
300
350
Temperature (C)
mixture analysis chemical purity physical purity (crystal forms, crystallinity) phase diagrams eutectic formation (interactions with other molecules)
Sample: INDIUM CRIMPED PAN CHECK Size: 7.6300 mg Method: indium Comment: P/N 56S-107 0.5
File: C:...\10C per min crimped\DSC010920A.3 Operator: Ron Vansickle Run Date: 20-Sep-01 09:13 Instrument: 2920 MDSC V2.6A
0.0
-0.5
-1.0
-1.5
-2.0
-2.5 140
Exo Up
145
150
155
160
165
170
175
Universal V3.3B TA Instruments
Temperature (C)
concave melting curve melting characterized at peak maxima eutectic impurities may produce a second peak
Glass Transitions
second-order transition characterized by change in heat capacity (no heat absorbed or evolved) transition from a disordered solid to a liquid appears as a step (endothermic direction) in the DSC curve a gradual volume or enthalpy change may occur, producing an endothermic peak superimposed on the glass transition
Sample: INDIUM CRIMPED PAN CHECK Size: 7.6300 mg Method: indium Comment: P/N 56S-107 0.5
Enthalpy of Fusion
DSC
156.50C 28.87J/g
File: C:...\10C per min crimped\DSC010920A.3 Operator: Ron Vansickle Run Date: 20-Sep-01 09:13 Instrument: 2920 MDSC V2.6A
0.0
-0.5
-1.0
-1.5
-2.0
157.81C
-2.5 140
Exo Up
145
150
155
160
165
170
175
Universal V3.3B TA Instruments
Temperature (C)
endothermic
Heat of Transition Rule endo-/exothermic solid-solid transition Heat of Fusion Rule higher melting form; lower Hf
endothermic
multiple thermal events leading to stable melt solid-solid transitions (A to B) from which the transition enthalpy ( HTR) can be measured*
Purity by DSC
eutectic impurities lower the melting point of a eutectic system purity determination by DSC based on Vant Hoff equation
Tm = To -
RTo2
Ho
97%
f
99%
applies to dilute solutions, i.e., nearly pure substances (purity 98%) 1-3 mg samples in hermetically-sealed pans are recommended polymorphism interferes with purity determination, especially when a transition occurs in the middle of the melting peak
benzoic acid
99.9%
Plato, C.; Glasgow, Jr., A.R. Anal. Chem., 1969, 41(2), 330-336.
DSC traces of a low melting polymorph collected at four different heating rates. (Burger, 1975)
0
2046742 FILE# 022511DSC.1
Lot A - pure
-1
-2
Lot B - seeds
-3
-4
-5 80
Exo Up
130
180
230
280
Universal V3.3B TA Instruments
Temperature (C)
Lot A: pure low melting polymorph melting observed Lot B: seeds of high melting polymorph induce solid-state transition below the melting temperature of the low melting polymorph
-0.1
Lot A
-0.3
-0.5
Lot B
-0.7
-0.9
DSC010622b.1 483518 HCL (POLYMORPH 1) DSC010622d.1 483518 HCL
-1.1 110
Exo Up
120
130
140
150
160
170
180
Universal V3.3B TA Instruments
Temperature (C)
although melting usually happens at a fixed temperature, solid-solid transition temperatures can vary greatly owing to the sluggishness of solid-state processes
0.2
-0.05
-0.10
0.0
-0.15
-0.20
Lot A
Lot A
-0.2
-0.25
-0.30
Lot B
-0.4
Lot B
-0.35
-0.40
-0.6
DSC010622b.1 483518 HCL (POLYMORPH 1) DSC010622d.1 483518 HCL
-0.45
-0.50 110
Exo Up
120
130
140
150
160
170
180
-0.8 110
120
130
140
150
160
170
180
Universal V3.3B TA Instruments
Temperature (C)
Temperature (C)
the variable melting point was related to the large stability difference between the two polymorphs; the system was driven to undergo both melting and solid-state conversion to the higher melting form
GON-GY, kJ/mole
Y Tt ON melting
eutectic melting
DSC Signal
ON
ON
Y ON Y Y ON Y
ON
pure forms
120
T, o C
80
100
(G1-G2)(Te1) = Hme2(Te2-Te1)/(xe2Te2) (G1-G2)(Te2) = Hme1(Te2-Te1)/(xe1Te1) Yu, L. J. Pharm. Sci., 1995, 84(8), 966-974. Yu, L. J. Am. Chem. Soc, 2000, 122, 585-591.
Hyphenated Techniques
thermal techniques alone are insufficient to prove the existence of polymorphs and solvates other techniques should be used, e.g., microscopy, diffraction, and spectroscopy development of hyphenated techniques for simultaneous analysis TG-DTA TG-DSC TG-FTIR TG-MS
evolved gas analysis (EGA)
Weight (%)
Sample: SODIUM TARTRATE (ALDRICH) Size: 6.1176 mg Method: 25C TO 300 Comment: LOT# 22411A0 120
15.55% (0.9513mg) 24.80C 100.0%
TGA-DTA
File: C:\TA\Data\Sdtcal\2004\TGA040105A.5 Operator: Ron Vansickle Run Date: 6-Jan-04 12:09 Instrument: 2960 SDT V3.0F
4.2
3.2
179.95C 84.45%
2.2
40
1.2
0.2 0 -0.8
-40 20
Exo Up
Temperature (C)
80
* whereas solid-solid transitions are generally too sluggish to be reversing at the time scale of the measurement, melting has a moderately strong reversing component
Recognizing Artifacts
sample pan distortion
shifting of Al pan
sensor contamination
RT changes