Continuous Manufacturing: Process Intensification Strategies in Synthesis, Workup and Formulation with a special focus on solids

Transcription

1 Continuous Manufacturing: Process Intensification Strategies in Synthesis, Workup and Formulation with a special focus on solids Dr. Dirk Kirschneck, Microinnova Engineering GmbH

2 Content Microinnova Overview Development Strategy for Flow Processes Characteristics of Flow Plant Design Case Study: Propoxylation N Case Study: Crystallization 2 Case Study: API-Plant

3 Microinnova Overview

4 7 Differentiators of Microinnova 1 Chemist and Engineer Interaction 3 End-to-End Continuous Manufacturing Competence Synthesis Work-up Formulation 6 2 Regulated Environment Experts for Continuous Manufacturing N Tons per 2 hour Competence Multi Process Intensification Technologies Projects/WPs Experience Flow Processing of Solids 7 Quelle: Google

5 specialists in process intensification process development engineering & plant We Continuous Microinnova focus processing our V-8combines customer s and process V-1 intensification knowledge and V-5 provide with tools, high V-2plant level as competence, micro solutions reactors, plug from flow independent the reactors, basic feasibility ultrasound from any study or other technologies technology to the are turnkey the or key supplier plant of success

6 Microinnova`s Approach to Success 1 st Milestone 2 nd Milestone 3 rd Milestone Process Design Phase I Phase II Phase III Fin The entire process design and development work until the final turnkey plant comprises of consecutive phases that enable a stepwise transfer of the existing process to a continuously realized process. A first Feasibility Optimization & Pilotphase plant sketch and cost estimation will be given after Phase I. Plant Phase: Basic Engineering Detailed Engineering 3D Plant design Plant assembly FAT Plant delivery - SAT

7 Phase I Process Design A successful business case study for a specific product requires Theoretical data of the process to rate the overall process performance Estimations of investment costs These informations will be available after the Process Design Phase I. Theoretical Evaluation Basic Lab Tests Process Flow Diagram Risk Assessment Phase II Feasibility Plant Cost Estimation

8 Focus on costs Getting Costs down Statement from BASF 1. Intensified Processes 2. Universal Engineering Designs costs/kg Better Control New Strategies volume/time T. Stammer (BASF) et al, CHISA 2014, Prague

9 Development Strategy for Flow Processes

10 How to design a flow process? Step 1: Evaluation of Drivers Step 2: Identification of Critical Parameters Selection of Tools Step 3:

11 Drivers for Flow and/or Microreactors

12 Application Profile Reactions Source Mass transfer Energy Conditions Environment Application A Application B

13 MIC Fish Methodology k 1 k 2 A + B C D k 4 F k 3 E k 1... desired standard reaction (solvent effect) k 2 follow up reaction (if late quench) k 3 side reaction (if C A C B ) k 4 decomposition (if high T) plug flow? high T, p? process liquid A? process gaseous A?

14 Technology Comparison Heat transfer Scalability Mass transfer Pressure drop Residence time Viscous fluids Mixing Solids handling Technology A Technology B

15 Process Intensification Toolbox

16 Towards perfect processing perfect mixing perfect heat exchange perfect residence time perfect mixing perfect heat exchange thermostat reaction zone 1 reaction zone 2 narrow residence time distribution no backmixing no hot spots reaction zone 3 no dead product zones ideal stoichiometry no high concentration spots V-8 product

17 QbD: Critical process parameter map Raw Material roast grade age of beans M M Milling Process Nparticle 2 size M distribution Extraction Process extraction time M extraction temperature extraction pressure M M CQA Crema too dark too light too less not stable

18 Out of the Box up to 400 C Liquid-Liquid Processes High Viscosity Gas- Catalytic Processes up to 50 bar up to 300 C Liquid-Solid Processes Precipitation Crystallization Liquid-Gas Processes Reactions with Cl 2 /HCL product Selfignition module by O2 Cryogenic Reactions 4 out of Generic TOP 10 High Corrosivity High exothermic reaction Customer examples 5 out of Pharma TOP 10 Chemical Global Players Polymer Companies Crop Protection Particle Surface Modification Continuous N Suspensions 2 (cat/solid educt) Melted Educt Reactions with O 2 /H 2 Ozone (plant) Reactions with NH 3 (liq) Very difficult Processes

19 Process Design Strategies

20 Example: selectivity increase Friedl-Crafts-Alkylation driver J. Yoshida, Flash Chemsitry, Wiley, 2008 toolbox

21 Example: Unstable reagents driver toolbox

22 Value by optimizing mass & heat transfer Operation Batch Flow Factor Reaction 20 min 20 min 1 Mass Transfer Heat Transfer 50 min 1 m 25 min 0,5 m 0,5 min 1 cm 0,5 min 1 cm

23 Technology Example: Extrusion Continuous generation of one substream of a Healthcare formulation Pharma Top10 Company

24 Polymer Projects Free Radical Polymerisation Modification of Functional Groups Cross Linking Endcapping Oligomer Synthesis N Formulation (e.g. Gel Structure) 2 Encapsulation (Interfacial area Polymerization)

25 Engineering

26 Engineering Competence Microinnova basic engineering detailed engineering 3D design V-8 automation solutions V-1 plant construction commissioning CE, ATEX, UL, UL-Ex, cgmp

27 Comparison batch versus conti / flow advantage batch flexibility multipurpose advantage conti/flow process performance safety easy automation process is adjusted to the plant plant is adjusted to the process concept necessary, which combines batch flexibility with continuous performance

28 On-module flexibility on-module adaption by exchanging specific parts engineered spaces for adaption reactor residence-time module

29 Modular plant design tank farm utilities-hub bus /plc electricity control air nitrogen heating + chilling utilities automation + supply control room µ feed 1 feed 2 feed 3 reactor 1 reactor 2 product production area module storage µ

30 System Architecture Automation

31 Scale up of flow processes Corning AFR Fluitec XR ESK MR IMM Star-Lam Flow Miniplant Level up to 10 l/hour Manufacturing Level up to l/hour

32 Case Study: Propoxylation

33 Case Study Propoxylation Exhaust gas Washing of exhaust gas Condenser PO Catalyst Solution Reaction (12h) Product N Dosing of alcohol 2 for reaction control PO Catalyst Alcohol Mixing Reaction (1min) Product Process Intensification Factor of ~700

34 Case study: Flow Miniplant Flow Miniplant Example of a 20 kg/h development or small scale production system

35 Case Study: Crystallization

36 Preferred particle size Flame retardant upper limit: mechanical properties of polymer lower limit: retardant behaviour Soluble salt upper limit: speed of solubility lower limit: dust formation

37 Cooling Crystallization Two-step-process 1. nucleation (seed generation) 2. growth of the particle

38 Case Study Flow Miniplant Continuous Crystallization

39 Continuous Crystallization Model Predictive Control product product From Perseptive Engineering

40 Multi-API Approach by Modules D. Ghislieri, K. Gilmore, P. Seeberger; Angew. Chem. Int. Ed. 2015, 54,

41 Continous Cryogenic API Plant Reaction: Continuous Solid Dosing into corrosive liquid under cryogenic conditions Residence time improved: - from 7 hours to 15 min Process V-17 safety V-15 increased Lossless scale-up

42 Unit operation: Filter-dryer Continuous Filtering & Drying

43 Services & Results

44 Summary process performance flexibility safety fast track realization turning process performance into money

45 Please contact me: