Thermal Analysis Technology

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Analises

Analises Térmicas

Térmicas Aplicadas

Aplicadas a

a

Fármacos

e

e Medicamentos

Medicamentos

e

e Medicamentos

Medicamentos

Faculdade de Farmácia

Faculdade de Farmácia –

– UFG

UFG

26 de setembro de 2009

Eng. Carlos Braga

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Algumas

Algumas aplicações

aplicações da

da Análise

Análise Térmica

Térmica na

na

Indústria

Indústria Farmacêutica

Farmacêutica

Determinação

Determinação de

de pureza

pureza

Caracterização

Caracterização de

de lipídeos

lipídeos e

e gorduras

gorduras

Polimorfismo

Thermal Analysis Technology

Polimorfismo

Tempo de

Tempo de prateleira

prateleira –

– shelf life

shelf life

Medidas

Medidas de

de quantidade

quantidade de

de umidade

umidade

Estabilidade

Estabilidade termo

termo--oxidativa

oxidativa

Interação

Interação entre

entre compostos

compostos ativos

ativos

Propriedades

Propriedades de tempo de

de tempo de liberação

liberação das

das cápsulas

cápsulas das

das drogas

drogas

Aparência

Aparência das

das cápsulas

cápsulas

Estudos

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Thermal Analysis Technology

TG/DTA 7200

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DSC7020

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Physical Change

Information

Melting

Melting point (Melting point (TmTm))

Melting enthalpy (Delta

Melting enthalpy (Delta HmHm) )

Crystallization

Crystallization temperature (Crystallization temperature (TcTc))

Crystallization enthalpy (Delta Crystallization enthalpy (Delta HcHc))

Glass Transition

Glass transition temperature (Glass transition temperature (TgTg))

DSC Applications

Glass Transition

Glass transition temperature (Glass transition temperature (TgTg))

Heat capacity change at

Heat capacity change at TgTg (Delta Cp)(Delta Cp)

Evaporation

Sublimation

Temperature Temperature

Magnetic Transition

Curie PointCurie Point

Specific Heat Capacity

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DSC Applications

Chemical Reaction

Information

Cure Reaction

Reaction temperatureReaction temperature Reaction enthalpy Reaction enthalpy

Oxidation Reaction

Decomposition

Chemisorption

Desorption

Chemisorption / desorption temperature Chemisorption / desorption temperature Chemisorption / desorption energy

Chemisorption / desorption energy

Others

Information

Micelle Formation

Krafft pointKrafft point Energy Energy

Thermal Denaturation

Thermal denaturation temperatureThermal denaturation temperature Thermal denaturation enthalpy Thermal denaturation enthalpy

Gelatinization

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Princípio de Operação do DSC 7020

Sensor Oval Amostra Referência

Heater

Oval Sensor Plate Sub Heat Sink

Main Heat Sink

Oval OvalOval

Oval DSCDSCDSC DiagramDSC DiagramDiagramDiagram

Main Heat Sink

Heat Filter

Lead Wire

Oval Oval Oval

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Sensor Oval

Amostra Referência

Princípio de Operação do DSC 7020

Main Heat Sink

Foto Foto Foto

Foto dodododo sensorsensorsensorsensor OvalOvalOvalOval DSCDSCDSCDSC

・

Alta Resolução

・

Baixa resistencia térmica pela 2ª dimensão de fluxo de calor

・

Baixa transferência de calor entre amostra e referencia

・

Baixo ruído

・

Heat sink substrate used as sensor holder also

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DSC7020

Module Module Module Module DSC7200 DSC Type DSC Type DSC Type

DSC Type Heat Flux

Temperature Range Temperature Range Temperature Range Temperature Range -160～～～～725℃℃℃℃ Temperature Reproducibility ±±±±0.1℃℃℃℃ Dynamic Range Dynamic Range Dynamic Range Dynamic Range ±±±±350mW RMS Noise/ Sensitivity RMS Noise/ Sensitivity RMS Noise/ Sensitivity RMS Noise/ Sensitivity 0.1µW/0.2µW Temperature Rate Temperature Rate Temperature Rate

Temperature Rate 0.01～～～～100℃℃℃℃_/min

Environment Environment Environment

Environment Air, Inert Gas

Sample Pan

Open （（（（Al））））100µｌｌｌｌ

Hermetic （（（（Al・・・・Alozine)

Sealed （（（（Al・・・・Ag・・・・SUS・・・・SUS ））））15µｌｌｌｌ

Gas Purge Control Mass Flow (Optional)

Gas Controller （（（（Optional））））

Cooling Unit Automatic LN2, Electronic Cooling

system, Air Cooling （（（（Optional））））

Auto-sampler 50 Positions, Mechanic Arm（（（（

Optional））））

Temperature Range

Automatic LN2 cooling unit：：：：-140～～～～ 725℃℃℃℃

Electronic Cooling system ：：：：-75～～～～550℃℃℃℃

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Performance Criteria

1. Stable baseline

2. High sensitivity

D S C µ W 500.0 250.0 0.0

3. High resolution

4. Reproducibility

Baseline performance is quantified by determining the amount

of curvature and drift over a specified temperature range

10C/min Temp. ℃ 100 50 0 -50 -250.0 -500.0 150 200 250 300

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℃ ℃ ℃ ℃ 159 158 157 156 155 154 153 D S C / u W 280 260 240 220 200 180 Indium：：：：0.003mg, 1C/min

Performance Criteria

1. Stable baseline

2. High sensitivity

Temp / ℃℃℃℃ 159 158 157 156 155 154 153

3. High resolution

4. Reproducibility

Temp / ℃℃℃℃ 140.0 120. 0 100.0 80.0 60.0 D S C / u W -300 -320 -340 -360 -380 -400 86.3 C Polystyrene：：：：0.18mg, 10C/min

DSC sensitivity is a function of the signal to noise ratio of the heat flow signal,

as well as baseline quality for step transitions

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Performance Criteria

1. Stable baseline

2. High sensitivity

3. High resolution

4. Reproducibility

・・・・Sample: Azoxyanisole ・・・・DSC：：：：DSC7020 ・・・・Sample weight：：：：5mg ・・・

・Scan Rate：：：：20ﾟﾟﾟﾟC/min

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Performance Criteria

1. Stable baseline

2. High sensitivity

3. High resolution

D S C m W 0.0 -10.0

3. High resolution

4. Reproducibility

Temp. ℃ 165.0 160.0 155.0 150.0 D S C m W -20.0 -30.0

In, n=5

10mg, 10C/min

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Acessórios

Automatic LN2

50 positions Auto-sampler

Gas Controller

Eletrônic Cooling System

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Sample Sealer & Sample Cup

••Easy Operation

Easy Operation

••High Reproducibility

High Reproducibility

Sample Cup 1-7 Sealed Type 8-15 Open Type 16-17 Hermetic Type Alumina Pan Alumina Pan Al Alodine Processed 15ml Al Alodine Processed 15ml Al Auto Al Auto--samplersampler Alumina Pan Alumina Pan

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Estudo de Pureza

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Estudo de Pureza

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Estudo de Polimorfismo

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Estudo de Polimorfismo

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TG/DTA 7200

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TG / DTA

(Simultaneous TG/DTA Measurement Analyzer)

•Horizontal Differential Type

•Type of Balance Beam: One Touch Approach (Could be exchange within 30 seconds).

•Possible for Heater Exchange and Supplement of Auto Sampler.

•Available with Auto Stepwise Isothermal Thermogravimetry

function(Controlled-Rate Thermal Analysis

、

CRTA).

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Pre

Pre--calibration Temp. Control Mode

calibration Temp. Control Mode

230C hold 230C hold 230C hold 230C hold T e m p. C T e m p. C T e m p. C T e m p. C Te m pe ra tu re ℃ 300.0 250.0 200.0 150.0 229.6℃ 229.5℃ 230℃ Hold Time/min Time/min Time/min Time/min T e m p. C T e m p. C T e m p. C T e m p. C 60.00 50.00 40.00 30.00 20.00 10.00 0.00 Te m pe ra tu re 150.0 100.0 50.0 0.0

Module

：

TG/DTA

、

DSC

、

TMA

、

DMA

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温度 ℃ 1000 800 600 Start

Forced Air Cooling

T e m p. C T e m p. C T e m p. C T e m p. C 時間 min15.00 20.00 25.00 10.00 5.00 0.00 温度 ℃ 400 200 0 Natural Cooling

Forced Air Cooling

Time/min Time/minTime/min Time/min T e m p. C T e m p. C T e m p. C T e m p. C DSC,TG/DTA,TMA,DMS

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T G % T G % T G % T G % 20.0 20.0 20.0 20.0 0.0 0.0 0.0 0.0 - 20.0 - 20.0 - 20.0 - 20.0 - 40.0 - 40.0 - 40.0 - 40.0 D T A u V D T A u V D T A u V D T A u V 25.0 25.025.0 25.0 20.0 20.020.0 20.0 15.0 15.015.0 15.0 10.0 10.010.0 10.0

High

High--sensitive Data

sensitive Data

0.1mg CaC

₂

O

₄

.H

₂

O

Temp ℃ Temp ℃Temp ℃ Temp ℃400.0400.0400.0400.0 600.0600.0600.0600.0 800.0800.0800.0800.0 200.0 200.0200.0 200.0 0.0 0.00.0 0.0 T G % T G % T G % T G % - 40.0 - 40.0 - 40.0 - 40.0 - 60.0 - 60.0 - 60.0 - 60.0 - 80.0 - 80.0 - 80.0 - 80.0 - 100.0 - 100.0 - 100.0 - 100.0 D T A u V D T A u V D T A u V D T A u V 10.0 10.010.0 10.0 5.0 5.05.0 5.0 0.0 0.00.0 0.0 - 5.0 - 5.0- 5.0 - 5.0

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TG/DTA Data

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D T G u g /m in 300.0 200.0 T G % 100.0 95.0 10.6%

Sulfato de Vincristina

Perda

Perda por secagem

por secagem

((norma Farmacopéia USP

norma Farmacopéia USP –

– Official

Official Monographs

Monographs))

10mg; 5°°°°C/min de 25°°°°C a 200°°°°C em N240mL/min, platô em 160°°°°C, perder no máximo 12%

Temp Cel 120.0 100.0 80.0 60.0 40.0 D T G u g /m in 100.0 0.0 T G % 90.0 85.0 80.0

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Start value

Stop value

CRTA : Controlled

CRTA : Controlled--Rate Thermal Analysis

Rate Thermal Analysis

Principle of CRTA

Ｔｅｍｐ．Ｔｅｍｐ．Ｔｅｍｐ．Ｔｅｍｐ． Stop value

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Automated Stepwise Temperature Control

Standard StandardStandard Standard Automated AutomatedAutomated Automated StepStepStepStep

Temp. C Standard Standard Standard Standard Automated Step

Automated StepAutomated Step

Automated Step

Sample

：

CuSO

₄

････

5H

₂

O

Temp. C Temp Temp. C

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Constant TG

Constant TG--rate Measurement

rate Measurement

Temp.

C

Sintering Process of Alumina

Temp.

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Research & Development Application

ー

DTG(TG) and DSC peak separation.

( for reaction of different activation energies )

ー

Data simulation of measurements that are difficult

such as extremely high (10

5

℃

_{/min ) or extremely low}

heating rates (10

-3

℃

_{/min ) .}

Application of Highway TA

℃

heating rates (10

-3

℃

_{/min ) .}

Reduced measurement time for Quality Control

ー

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Principle of Highway TA

ｌ

ｏ

ｇ

ｌ

ｏ

ｇ

ｌ

ｏ

ｇ

ｌ

ｏ

ｇ

ＢＢＢＢ

High Heating Rate data

Heating Rate of measurement

Highway TA Conversion Principle

T : Temp. B : Heating Rate

１／Ｔ

ＢＢＢＢ

Slope

→ ∆

Ｅ

Low Heating

Rate data

Heating Rate of measurement

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ＴＧ

Raw data

100℃/

min

Highway TA

ＤＴＧ

100℃/

min

Simulation data

10℃/min

Temp. / ℃

CaC

2

O

4

･

･･

･

H

2

O

(35)

Highway TA

＜

LDPE

＞

(36)

Data of Gypsum

Highway TA

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1 0 0 . 0 9 8 . 0 9 6 . 0

Highway TA

15°°°°C/min 20°°°°C/min 30°°°°C/min

Sulfato de Vincristina

T e m p C e l 1 4 0 . 0 1 2 0 . 0 1 0 0 . 0 8 0 . 0 6 0 . 0 4 0 . 0 T G % _{9 4 . 0} 9 2 . 0 9 0 . 0 8 8 . 0 5°°°°C/min 10°°°°C/min 50°°°°C/min

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SII ゜ EXSTAR 6000

TG/DTA

Temp. Controller

MS

TG/DTA furnace with temp. maintenance heater Gas Transfer Tube