EYP 2006 EYP 2006 Differential Scanning Differential Scanning Calorimetry Calorimetry Clare Rawlinson Clare Rawlinson School of Pharmacy School of Pharmacy University of Bradford University of Bradford “ “ Cooking with Chemicals Cooking with Chemicals ” ” EYP 2006 EYP 2006 Outline Outline   Brief history of thermal analysis Brief history of thermal analysis   Theory of thermal analysis techniques Theory of thermal analysis techniques – – Thermal Gravimetric Analysis (TGA) Thermal Gravimetric Analysis (TGA) – – Differential Scanning Calorimetry (DSC) Differential Scanning Calorimetry (DSC)   Generating valid data Gener ating valid data – – Calibration Calibration – – Sample preparation Sample preparation   Interpreting data and Applications Interpreting data and Applications – – Real events Real events – – Artefacts Artefacts   Recent advances Recent advances EYP 2006 EYP 2006 Calorimetry Calorimetry   Calorimetry Calorimetry – – The study of heat transfer during The study of heat transfer during physical and chemical processes physical and chemical processes   Calorimeter Calorimeter – – A device for measuring the heat A device for measuring the heat transferred transferred Lavoisier Lavoisier and and Laplace Laplace (1782 (1782 - - 1784): 1784):   oil was burned in a lamp ( oil was burned in a lamp ( Fig 9 Fig 9 ) held in ) held in a bucket (Fig. 8) held in a wire mesh a bucket (Fig. 8) held in a wire mesh cage ( cage ( f f ) )   surrounded by ice in spaces surrounded by ice in spaces b b and and a a of of the double walled container a foot in the double walled container a foot in diameter diameter   lid ( lid ( F F ) was topped with ice, as was a ) was topped with ice, as was a mesh lid (not shown) beneath it that mesh lid (not shown) beneath it that covered the inner volume covered the inner volume b b EYP 2006 EYP 2006 Oil lamps to Guinea Pigs Oil lamps to Guinea Pigs … …   Measured heat production of Measured heat production of the metabolic processes in the metabolic processes in the ice bath calorimeter the ice bath calorimeter   Outer jacket prevented Outer jacket prevented conduction of heat from the conduction of heat from the external environment which external environment which would have also melted the would have also melted the ice ice   From latent heat of fusion for From latent heat of fusion for ice (334 J/gram ice at 0 ice (334 J/gram ice at 0 º º C) C) Lavoisier Lavoisier converted the rate converted the rate of water formation to heat of water formation to heat production production   In 10 hours 370 grams of ice In 10 hours 370 grams of ice melted melted Guinea pig produced 12,358 J per hour of heat Guinea pig produced 12,358 J per hour of heat (12.4 kJ/hr) (12.4 kJ/hr) EYP 2006 EYP 2006 Basic Principles of Thermal Analysis Modern instrumentation used for thermal analysis usually consists of four parts:  sample/sample holder  sensors to detect/measure a property of the sample and the temperature  an enclosure within which the experimental parameters may be controlled  a computer to control data collection and processing EYP 2006 EYP 2006 TGA and DSC TGA and DSC  Thermogravimetric Analysis (TGA) – – mass change of a substance measured as function of mass change of a substance measured as function of temperature whilst the substance is subjected to a controlled temperature whilst the substance is subjec ted to a controlled temperature programme temperature programme 1 1 – – mass is lost if the substance contains a volatile fraction mass is lost if the substance contains a volatile fraction  Differential Scanning Calorimetry (DSC) – – provides information about thermal changes that do not involve a provides information about thermal changes that do not involve a change in sample mass change in sample mass 1 1 – – more commonly used technique than TGA more commonly used technique than TGA – Two basic types of DSC instruments: heat-flux and power compensation 1 Haines, P. J. (2002) The Royal Society of Chemistry, Cambridge. EYP 2006 EYP 2006 Sample holder :  sample and reference are connected by a low-resistance heat flow path  Aluminium, stainless, platinum sample pans Sensors: Sensors:   temperature sensors temperature sensors   usually thermocouples usually thermocouples Furnace:  one block for both sample and reference cells Temperature controller: • temperature difference between the sample and reference is measured Heat Flux DSC sample pan inert gas vacuum heating coil reference pan thermocouples EYP 2006 EYP 2006 Sample holder Sample holder : :   Aluminium Aluminium , platinum, stainless steel pans , platinum, stainless steel pans Sensors: Sensors:   Pt resistance Pt resistance thermocouples. thermocouples.   Separate sensors Separate sensors and heaters for the and heaters for the sample and reference sample and reference Furnace: Furnace:   separate blocks for sample and reference cells separate blocks for sample and reference cells Temperature controller: Temperature controller:   differential thermal power is supplied to the heaters to mainta differential thermal power is supplied to the heaters to mainta in the in the temperature of the sample and reference at the program value temperature of the sample and reference at the program value sample pan ΔT = 0 inert gas vacuum inert gas vacuum individual heaters reference pan thermocouple Power Compensated DSC Power Compensated DSC EYP 2006 EYP 2006 Outline Outline   Brief history of thermal analysis Brief history of thermal analysis   Theory of thermal analysis techniques Theory of thermal analysis techniques – – Thermal Gravimetric Analysis (TGA) Thermal Gravimetric Analysis (TGA) – – Differential Scanning Calorimetry (DSC) Differential Scanning Calorimetry (DSC)   Generating valid data Gener ating valid data – – Calibration Calibration – – Sample preparation Sample preparation   Interpreting data and Applications Interpreting data and Applications – – Real events Real events – – Artefacts Artefacts   Recent advances Recent advances EYP 2006 EYP 2006 DSC Calibration Baseline Calibration  evaluation of the thermal resistance of the sample and reference sensors  measurements over the temperature range of interest [...]... etc.) are kinetic so shift to higher temp when heated at a higher rate increasing the scanning rate increases sensitivity, while decreasing the scanning rate increases resolution to obtain thermal event temperatures close to the true thermodynamic value, slow scanning rates (e.g., 1–5 K/min) should be used Rapid scanning can obscure thermal events Advantageous in fast scan DSC, e.g 500K/min EYP 2006... of thermal analysis techniques – Thermal Gravimetric Analysis (TGA) – Differential Scanning Calorimetry (DSC) Generating valid data – Calibration – Sample preparation Interpreting data and Applications – Real events – Artefacts Recent advances EYP 2006 Microcalorimetry High sensitivity DSC Solutions Scan range typically 0-120 °C Scanning rate of 0-120 °C/hr Reverse scan rate 0-45 °C/hr (depending on... carbonate Removes waste products from sublimation or decomposition EYP 2006 Outline Brief history of thermal analysis Theory of thermal analysis techniques – Thermal Gravimetric Analysis (TGA) – Differential Scanning Calorimetry (DSC) Generating valid data – Calibration – Sample preparation Interpreting data and Applications – Real events – Artefacts Recent advances EYP 2006 Typical Features of a DSC... slow scanning speeds (Unless aiming to obscure thermal transitions, e.g fast scan DSC) avoid decomposition in the DSC (Run TGA first – its easier to clean up!) EYP 2006 Caution… It is a bulk tool – Analysing the gross average of events in a sample – Conversely, small powder sample in DSC may not represent packing of powder bulk in decomposition studies Instrument error in DSC typically ± 0.5 - 1ºC In Scanning. .. (POLYMORPH 1) DSC010622d.1 483518 HCL 140 150 Temperature (°C) 160 170 180 Universal V3.3B TA -0.8 110 Exo Up EYP 2006 120 130 140 150 Temperature (°C) 160 170 180 Universal V3.3B TA ‘Hyper’ DSC Fast scanning DSC Only possible with power compensated Normal equipment ≈ 100 ºC/min Specialised up to 500 ºC/min Increased sensitivity, loss of resolution e.g amorphous content in mainly crystalline sample . EYP 2006 EYP 2006 Differential Scanning Differential Scanning Calorimetry Calorimetry Clare Rawlinson Clare Rawlinson School of Pharmacy School. – – Thermal Gravimetric Analysis (TGA) Thermal Gravimetric Analysis (TGA) – – Differential Scanning Calorimetry (DSC) Differential Scanning Calorimetry (DSC)   Generating valid data Gener ating valid. – – Thermal Gravimetric Analysis (TGA) Thermal Gravimetric Analysis (TGA) – – Differential Scanning Calorimetry (DSC) Differential Scanning Calorimetry (DSC)   Generating valid data Gener ating valid