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- In the research and development process of innovative drugs, the chemical process research of drugs plays a pivotal role. During the synthesis process to the scale up process in the laboratory, it is not only about output, but also various errors and risks. Therefore, in the development of innovative drugs, the assessment of the safety of chemical processes and equipment is extremely important.In January 2017, the State Administration of Work Safety issued the instructions and guidelines on strengthening the safety risk assessment of fine chemical reactions.Enterprises involved in the key supervision of hazardous chemical processes and Grignard reactions, intermittent and semi-batch reactions of metal organic synthesis reactions, in any of the following situations, must carry out a reaction safety risk assessment:The new technology and formula used for the first time in China for industrial production and the new process introduced for the first time from overseas and the reaction safety risk assessment has not been carried out. The existing process route, process parameters or device capabilities are changed, and the safety risk assessment report is not filed. Production safety accidents have been occurred due to reaction process issues.Adhering to “Innovation-Driven, Quality First”, Medicilon has established a laboratory research platform focused on evaluating the safety of chemical processes to provide clients with customized, accurate and reliable testing data and safety assessments.
Safety Assessment ProcessTarget Reaction Calorimetry Research on secondary reactions (thermal stability) of raw materials, intermediates and products RC1 DSC Measure Various Thermal Data Thermal Process Detection of Chemical Raw Materials Heat Generation Rate The heat absorption and release, melting point, decomposition temperature, decomposition rate and heat release of a single chemical during the heating process. Heat of Reaction Reaction Progress Thermal Process Detection of Chemical Process System Starting Point, Ending Point & Dynamics Reduce the system to the DSC test system according to the actual ratio, test the decomposition temperature, decomposition rate and decomposition heat of the entire system Process Safety and Scale-Up Kinetic Process of Ddecomposition Reaction Determination of Adiabatic Temperature Rise Maximum Temperature MTSR Heat Conversion Rate Specific Heat Capacity Cp Heat Transfer Coefficient: U Heat Accumulation vs Time Curve TD24, Activation Energy Ea, Pre-reference Factor A, Predict and Evaluate the Safety of Chemical Reactions Fully Automatic Control Mixing\Feeding\Pressure\PH Control High Hr, Fast Kinetics High Risk Low Risk Trigger a second reaction? No further testing required Adiabatic Test ARC Starting Temperature; Pressure Data; Adiabatic Temperature Rise; TMRad; Heat Release; TD24; Heat Release Rate Levels of Danger Process Risk Actions Needed Level 1 & Level 2 Low Process Risk No Actions Needed Level 3 & Level 4 Process is Danger Technical Actions Needed Level 5 High Process Risk Redesign the Process
Safety Assessment Laboratory- Automatic Reaction Calorimeter RC1mx（Model: METTLER TOLEDO RC1mx）
AP01 - Atmospheric
Temperature: -73 - 230
Reaction Volume: 0.5L
Pressure: 50m bar (Atmospheric)HP60 - Autoclave
Temperature: -10 - 250
Volume: 1.5L
Pressure: 60 barRC1 Reaction Calorimetry Test Data list Reaction Temperature Tp(℃) 48 Reaction System Quality Mr(g) 230.7 Heat Transfer Coefficient U(W.k-1m-2) Before Reaction 177.5 After Reaction 190.4 Specific Heat Capacity of Reaction Material Cp(J.g-1.k-1) Before Reaction 2.9843 After Reaction 3.4922 Temperature Difference between Reactor and Jacket Tr-Tj(k) 2.7 Maximum Specific Heat Release Rate q’max(w.kg-1) 49.0 Reaction Heat Accumulation Acc(%) 5.7 Reaction Heat Release Q(kJ) 83.2 Reaction Heat Release RatioQ’(KJ.kg-1) 360.6 Molar Reaction Enthalpy-△Hr(kJ.mol-1) 213.3 (Calculated based on the molar amount of benzonitrile input) Adiabatic Temperature Rise△Tad(K) 103.2 Highest Temperature for Synthesis Reaction MTSR（℃） 54.1 Highest temperature when the Heat Accumulation Degree is 100% for Synthesis Reaction（℃） 151.2 - Differential Scanning Calorimeter DSC
DSC Test Data
Decomposition Heat Evaluation ListDecomposition Heat (j/g) Description 1 Decomposition Heat < 400 Potential Explosion Hazard 2 400 < 1200 < 1200 < Decomposition Heat < 1200 The release of heat is large, and the potential explosion risk is high 3 1200 < 3000 < 3000 < Decomposition Heat < 3000 Large heat release, high potential explosion risk 4 Decomposition Heat>3000 The release of heat is very large, and the potential explosion risk is very high Sample Size (mg) 8.872 Heat Release (mJ) 1141.80 Specific Heat 128.70 Initial Decomposition Temperature 147.12 Pre-reference Factor 20.04+/-0.29/td> Reaction Activation Energy 91.29+/-1.01 Reaction Level 0.87+/-22.04e-03 TMRad (min) TD24 57.4 - Adiabatic Accelerating Calorimeter ARC
ARC Test Chart and Data
Temperature/Pressure – Antoine Equation Curve
TMR Fitting CurveInitial Exothermic Temperature 114.5 Initial Temperature Rising Rate 0.022 Maximum Temperature Rising Rate Temperature 188 Maximum Temperature Rising Rate 10.904 Maximum Pressure Rising Rate 14.687 Maximum Temperature 197.1 Maximum Pressure 53.277 Adiabatic Temperature Rise 82.6 Heat Release 1247.47 Specific Heat 207.912 TD24 103.6 Reaction Level 0.84 Activation Energy 160867
