Thermal Analysis Technology

Analises Térmicas Aplicadas a Fármacos e Medicamentos Faculdade de Farmácia UFG 26 de setembro de 2009 Eng. Carlos Braga

Thermal Analysis Technology Algumas aplicações da Análise Térmica na Indústria Farmacêutica Determinação de pureza Caracterização de lipídeos e gorduras Polimorfismo Tempo de prateleira shelf life Medidas de quantidade de umidade Estabilidade termo-oxidativa oxidativa Interação entre compostos ativos Propriedades de tempo de liberação das cápsulas das drogas Aparência das cápsulas Estudos de liofilização ou Freeze drying

Thermal Analysis Technology TG/DTA 7200 DSC 7020

EXSTAR SERIES Thermal Analyzer DSC7020

DSC Applications Physical Change Information Melting Melting point (Tm) Melting enthalpy (Delta Hm) Crystallization Crystallization temperature (Tc) Crystallization enthalpy (Delta Hc) Glass Transition Glass transition temperature ( Evaporation Sublimation Magnetic Transition Specific Heat Capacity Glass transition temperature (Tg Tg) Heat capacity change at Tg (Delta Cp) Temperature Curie Point Specific Heat Capacity (Cp)

DSC Applications Chemical Reaction Cure Reaction Oxidation Reaction Decomposition Chemisorption Desorption Others Micelle Formation Thermal Denaturation Gelatinization Information Reaction temperature Reaction enthalpy Reaction temperature Reaction enthalpy Reaction temperature Reaction enthalpy Chemisorption / desorption temperature Chemisorption / desorption energy Information Krafft point Energy Thermal denaturation temperature Thermal denaturation enthalpy Gelation point

Princípio de Operação do DSC 7020 Referência Sensor Oval Amostra Heater Sub Heat Sink Oval Sensor Plate Main Heat Sink Oval DSC Diagram Main Heat Sink Lead Wire Heat Filter Oval DSC Cross Section

Princípio de Operação do DSC 7020 Sensor Oval Referência Amostra Main Heat Sink Foto do sensor Oval DSC 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 Filter stored inside sensor in order to cut the noise.

DSC7020 Module DSC Type Temperature Range Temperature Reproducibility Dynamic Range RMS Noise/ Sensitivity Temperature Rate Environment Sample Pan Gas Purge Control Cooling Unit Auto-sampler Temperature Range DSC7200 Heat Flux -160~725 ±0.1 ±350mW 0.1µW/0.2µW 0.01~100 /min Air, Inert Gas Open (Al) 100µl Hermetic (Al Alozine) Sealed (Al Ag SUS SUS )15µl Mass Flow (Optional) Gas Controller (Optional) Automatic LN2, Electronic Cooling system, Air Cooling (Optional) 50 Positions, Mechanic Arm( Optional) Automatic LN2 cooling unit:-140~ 725 Electronic Cooling system :-75~550 Air Cooling :Ambient~725

Performance Criteria 500.0 1.Stable baseline 250.0 2.High sensitivity 3. High resolution DSC µw 0.0-250.0 4. Reproducibility -500.0-50 10C/min 0 50 100 150 200 250 300 Temp. Baseline performance is quantified by determining the amount of curvature and drift over a specified temperature range

Performance Criteria 280 260 Indium:0.003mg, 1C/min 1.Stable baseline DSC / uw 240 220 2. High sensitivity 3. High resolution 4. Reproducibility DSC/ uw 200 180 153-300 -320-340 -360 154 155 156 157 Temp / 86.3 C 158 159-380 -400 60.0 Polystyrene:0.18mg, 10C/min 80.0 100.0 Temp / 120. 0 140.0 DSC sensitivity is a function of the signal to noise ratio of the heat flow signal, as well as baseline quality for step transitions

Performance Criteria 1.Stable baseline 2.High sensitivity 3.High resolution 4. Reproducibility Resolution=1.8 Sample: Azoxyanisole DSC:DSC7020 Sample weight:5mg Scan Rate:20 C/min

Performance Criteria 1.Stable baseline 2.High sensitivity 3.High resolution 4.Reproducibility DSC mw 0.0-10.0-20.0 In, n=5 10mg, 10C/min -30.0 150.0 155.0 160.0 165.0 Temp.

Acessórios 50 positions Auto-sampler Automatic LN2 Gas Controller Cooling Can Eletrônic Cooling System

Sample Sealer & Sample Cup Easy Operation High Reproducibility Sample Cup 1-7 Sealed Type 8-15 Open Type 16-17 Hermetic Type Alumina Pan Al Alodine Processed 15ml Al Auto-sampler Alumina Pan

Estudo de Pureza

Estudo de Pureza

Estudo de Polimorfismo

Estudo de Polimorfismo

EXSTAR SERIES Thermal Analyzer TG/DTA 7200

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). Compatible with FT-IR,MS,GC-MS multiple measurement.

TG/DTA Diagram

Pre-calibration Temp. Control Mode 300.0 250.0 230 230C Hold hold 200.0 229.5 229.6 Temperature Temp. C 150.0 100.0 Module:TG/DTA DSC TMA DMA 50.0 0.0 0.00 10.00 20.00 30.00 40.00 50.00 60.00 Time/min

Forced Air Cooling 1000 800 Start 温 Temp. 度 C Temp. C 600 400 Natural Cooling DSC,TG/DTA,TMA,DMS 200 Forced Air Cooling 0 0.00 5.00 10.00 15.00 時 Time/min 間 min 20.00 25.00

High-sensitive Data 20.0 0.0 0.1mg CaC 2 O 4.H 2 O 25.0 20.0-20.0 15.0 TG % - 40.0 10.0 DTA uv - 60.0 5.0-80.0 0.0-100.0 0.0 200.0 400.0 Temp 600.0-5.0 800.0

TG/DTA Data <Kaolinite>

Perda por secagem (norma Farmacopéia USP Official Monographs) 100.0 Sulfato de Vincristina 300.0 TG % 95.0 90.0 10.6% 200.0 100.0 DTG ug/min 85.0 0.0 80.0 40.0 60.0 80.0 Temp Cel 100.0 120.0 10mg; 5 C/min de 25 C a 200 C em N2 40mL/min, platô em 160 C, perder no máximo 12%

CRTA : Controlled-Rate Thermal Analysis Start value Stop value Temp. Principle of CRTA

Automated Stepwise Temperature Control Automated Step Standard Temp. C Standard Automated Step Temp Temp. C Sample:CuSO 4 5H 2 O

Constant TG-rate Measurement Temp. C Sintering Process of Alumina

Application of Highway TA 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 ). Reduced measurement time for Quality Control ー Measurement time 1/2~1/10

Principle of Highway TA l o g High Heating Rate data B Heating Rate of measurement Slope E 1/T Low Heating Rate data Highway TA Conversion Principle T : Temp. B : Heating Rate

Highway TA TG DTG Raw data 100 /min Simulation data 10 /min Temp. / CaC 2 O 4 H 2 O Heating rate : 100 /min 10 /min

Highway TA <LDPE>

Highway TA Data of Gypsum CaS0 4 2H 2 O+ CaS0 4 1/2H 2 O

Highway TA 1 0 0. 0 9 8. 0 9 6. 0 15 C/min 20 C/min Sulfato de Vincristina 30 C/min TG % 9 4. 0 10 C/min 50 C/min 9 2. 0 9 0. 0 5 C/min 8 8. 0 4 0. 0 6 0. 0 8 0. 0 1 0 0. 0 T e m p C e l 1 2 0. 0 1 4 0. 0

Multiple Thermal Analysis (Gas Trancefer System) Gas Transfer Tube MS SII EXSTAR 6000 TG/DTA TG/DTA furnace with temp. maintenance heater Temp. Controller TG/DTA - MS System Enable identification of gas evolved from TG. Gas Transfer System like FT-IR,MS,GC/MS could be selected.

TG-FTIR DATA of ABS TG of ABS IR Spectrum

TG-MS Data of CaC2O4.H2O TG/DTA of CaC 2 O 4 H 2 O Heating rate : 40 /min MS Spectrum 3rd step decomposition

TG-GC GC-MS Data of Wrap Film 50 ~ 200 200 300 310 MS Spectrum 300 ~ 310 TG / DTA

Obrigado!! Carlos Braga braga@srgrupo.com.br www.analisestermicas.com.br