Stirred Tank Scale-Up
Transcription
Stirred Tank Scale-Up
Stirred Tank Scale-Up An (ex-) Practitioner’s View MemTide Process Development Course London, 23-24 February 2012 Dr. Clemens Brechtelsbauer Principal Teaching Fellow Department of Chemical Engineering Imperial College London [email protected] Contents Further Reading The Design Environment Manufacturing steps Unit operations The design base Mixing Vessels, impellers and baffles Flow regimes Power draw Scale-Up Similarity concept Scale-up rules Multiphase systems Dr. Clemens Brechtelsbauer Slide 2 Stirred Tank Scale-Up Further Reading Edward L. Paul, Victor A. Atiemo-Obeng, Suzanne M. Kresta (Eds.) Handbook of Industrial Mixing John Wiley & Sons, 2004 Ekato Ruehr- und Mischtechnik GmbH Ekato Handbook of Mixing Technology Ekato GmbH, 2000 John H. Atherton, Keith J. Carpenter Process Development: Physicochemical Concepts Oxford University Press, 1999 Dr. Clemens Brechtelsbauer Slide 3 Stirred Tank Scale-Up Steps in API/Fine Chem Manufacture Risk Scale Dr. Clemens Brechtelsbauer Slide 4 Stirred Tank Scale-Up Unit Operations Particle Forming Unit Operations Chemistry: Reactions and Separations Reactions • Kinetics • Multiphase Separations • Distillation • Extraction Environmental • Mass Balance • Recovery Crystallisation • Scale-up Isolation • Filtration • Centrifuges Drying • FilterDryers Reaction Extraction Distillation Crystallisation Filtration Drying Dr. Clemens Brechtelsbauer Slide 5 Stirred Tank Scale-Up The Nature of the Beast Process = Chemistry + Physics Equipment Or “chemical rate constants are scale independent, whereas physical parameters are not” John H. Atherton Author of “Process Development: Physicochemical Concepts” Simply put: “Ye cannae change the laws of physics, Jim!” Dr. Clemens Brechtelsbauer Slide 6 Stirred Tank Scale-Up Standard Vessel Geometry B = T/10 H=T D C=T/3 T Dr. Clemens Brechtelsbauer Slide 7 Stirred Tank Scale-Up Ship’s Wheel vs. Cartwheel High shear Good for dispersions Low shear Good for solid suspension Dr. Clemens Brechtelsbauer Slide 8 Stirred Tank Scale-Up Beware of the Dork Side Minimum Stir and Mixing Volumes D V(stir, min) / V(mix, min) [L] 1200 1000 800 600 V stir min [L] 400 V mix min [L] 200 0 0 500 1000 1500 2000 2500 3000 Nominal vessel volume [L] D 1% V nominal V stir, min 5 % V nominal 7% V nominal V static V dish V mix, min 30-40 % V nominal Dr. Clemens Brechtelsbauer “Minimum stirred volume” does not mean “Minimum mixed volume” Slide 9 Stirred Tank Scale-Up Impeller Types Radial flow impeller Discharges liquid radially outwards towards vessel walls • Transitional & turbulent regime • Good for dispersing Axial flow impeller Discharges liquid axially towards base or liquid surface depending on rotation direction • Transitional & turbulent regime • Good for blending & suspending Mixed flow impeller Flow predominantly in axial direction with also a radial component • Transitional & turbulent regime • Good for blending, suspending & dispersing Close clearance impeller Ensures good motion near vessel walls • Laminar regime • Good for blending Dr. Clemens Brechtelsbauer Slide 10 Stirred Tank Scale-Up Understanding the Force In a stirred vessel, the presence of baffles is essential to convert the vortexing motion of the impeller into top to bottom mixing. No baffles is worst. Partial baffling is better. Full baffling is best. Baffles are needed to promote the flow pattern characteristic of the impeller type 4 Baffles, typical width T/12 (US) or T/10 (EU) with wall gap to prevent solids build-up Beavertail and finger baffles are often used in glass-lined vessels Dr. Clemens Brechtelsbauer Slide 11 Stirred Tank Scale-Up Power Draw The power drawn by an impeller is expressed through a power number equation: P = Po ρ N3 D5 Power number Po, or Newton number, Ne Depends on • Impeller type • Impeller and vessel DE/V dimensions • Properties of the phases present Must be measured! Dr. Clemens Brechtelsbauer Slide 12 E1/V A1, v1, h1, p1 A2, v2, h2, p2 E2/V Stirred Tank Scale-Up Flow Regimes Different parts of a vessel can experience different flow conditions Assess by Reynolds number N D2 Inertial Force Re Frictional Force The “power curve” Po vs Re can be used to evaluate the flow regime for the whole process Laminar: Re < 10 • Po Re-1 Transitional: 10 < Re < 103 • Po = f(Re) Turbulent: Re > 103 Ekato Handbook of Mixing Technology, p. 15 • Po = constant Dr. Clemens Brechtelsbauer Slide 13 Stirred Tank Scale-Up Geometric Similarity A single scale ratio, s, defines the relative magnitude of all linear dimensions between the large and small scale: H1 D1 C1 D2 T2 H 2 C2 s D1 T1 H1 C1 H2 D2 T1 T2 Dr. Clemens Brechtelsbauer Slide 14 Stirred Tank Scale-Up C2 Kinematic & Dynamic Similarity Kinematic Similarity Dynamic Similarity Velocities at geometrically similar positions remain constant • Constant tip speed • Constant superficial gas velocity • Constant maximum liquid velocity in impeller discharge Dr. Clemens Brechtelsbauer Slide 15 Ratio of forces (dimensionless groups) remain constant at different scales • Beware: – The relationship between process performance and the dimensionless group may not be linear! Stirred Tank Scale-Up Process Requirements A process may be controlled by one or more of: Liquid blending • reaction • homogenisation Solid-liquid mixing • solid catalysed reaction • dispersion Gas-liquid mixing • fermentation • hydrogenation Dispersing immiscible liquid • reaction • emulsions Heat transfer Defining controlling duty is key to successful scale-up! Dr. Clemens Brechtelsbauer Slide 16 Stirred Tank Scale-Up Scale-Up Rules Geometrically similar vessels Turbulent regime Process Rule Constant Parameter Liquid blending Equal tip speed ND Solid suspension Zwietering Njs D0.85 Solid distribution Equal energy input P/V Gas-liquid Equal mass transfer P / V (= kLa) Heat transfer Equal Re N D2 Fast reactions Equal mixing time N Dr. Clemens Brechtelsbauer Slide 17 Stirred Tank Scale-Up Scale-Up Decisions (1) Constant Mixing Time (2) Constant P/V (3) Just suspension (4) Tip speed (5) Reynolds number Note: • Criteria are mutually exclusive • On scale-up, impeller speed goes down Scale-up experiments and modelling essential! Dr. Clemens Brechtelsbauer Slide 18 Stirred Tank Scale-Up Future Multi-Purpose Plants Mixing design by function Principles Focused diversity by unit operation Multi-flight agitation Vessel types A: Reactor with work-up B: Reactor / crystalliser C: Crystalliser D: Reactor / hydrogenator E: Hydrogenator Physical properties determine process design envelope Implemented at GSK Dr. Clemens Brechtelsbauer A B C D E Slide 19 Stirred Tank Scale-Up Multiphase Systems Scale-Up Scale-down Study Process Assessment Continuous Improvement Scale-up Projection Plant Supplies Campaign Dr. Clemens Brechtelsbauer Slide 20 Stirred Tank Scale-Up Process Assessment Respiratory portfolio, final stage re-crystallisation Important for process success: Minimisation of variability on scale-up of “particle forming step” Reproducible, narrow particle size distribution • Homogeneous growth conditions to promote particle uniformity • Low shear to prevent attrition Initial hydro-dynamic simulation of flow profile by CFD for pilot and plant vessels 1500 L Pilot Plant Dr. Clemens Brechtelsbauer 4000 L Manufacturing Slide 21 Stirred Tank Scale-Up Scale-Down Study To determine the effect of shear & suspension on particle size & distribution, which cannot be predicted through CFD 2 L conical base lab reactor set up to scale-down manufacturing reactor Effect of improved suspension: No effect on particle size Effect of shear: No effect on particle size or distribution (PSD) Dr. Clemens Brechtelsbauer Slide 22 Stirred Tank Scale-Up Scale-Up Projection Just suspension speed determined experimentally for 2L lab reactor CFD multi-phase Lab, 2 L, 400 RPM Pilot Plant, 1500 L, 60-70 RPM simulation based on experimental stirrer speed: Plant operating impeller speeds recommended to maintain homogeneous suspension Stevenage pilot plant (1500 L): 60-70 RPM prevent risk of settling provide homogeneous growth conditions verify negligible shear effect Dr. Clemens Brechtelsbauer Slide 23 Stirred Tank Scale-Up Plant Supplies Campaign Analysis of lab and pilot plant results by different scale-up parameters solid suspension shear overall energy input Shear and energy input have no effect on particle size Increased suspension on scale-up: no effect on particle size slightly narrower PSD Penney Diagram 1000 Scale-up by constant mixing time [microns] 100 (P/V) l arge / (P/V) l ab energy input solid suspension 10 shear heat transfer 1 0.1 0.01 1.00E+00 1.00E+01 1.00E+02 1.00E+03 1.00E+04 Vplant / Vlab Dr. Clemens Brechtelsbauer Slide 24 Stirred Tank Scale-Up Process Assessment Jurong V460 (4000 L), 48 RPM Extrapolation to Manufacturing: Dr. Clemens Brechtelsbauer Slide 25 Stirred Tank Scale-Up The Voice of Scale-Up Experience Do Don’t Add solids to a reaction Evaporate to dryness Use “all in & heat” Rely on critical timing Do hot filtrations Risk all in one batch Collaborate Log Sample Safety test & review Use test Keep it simple McConville, F. X., CEP 103 (2007) 18-19 Dr. Clemens Brechtelsbauer Slide 26 Stirred Tank Scale-Up As Clear as Mud? "No one will believe you solved this problem in one day! We've been working on it for months. Now, go act busy for a few weeks and I'll let you know when it's time to tell them." (R&D supervisor, Minnesota Mining and Manufacturing/3M Corp.) Dr. Clemens Brechtelsbauer Slide 27 Stirred Tank Scale-Up