Secondary nucleation: observations, mechanisms, questions

Transcription

1 Secondary nucleation: observations, mechanisms, questions Jan Sefcik Centre for Continuous Manufacturing & Crystallisation & Department of Chemical and Process Engineering University of Strathclyde Glasgow

2 Primary and secondary nucleation nucleation primary secondary homogeneous heterogeneous Supersaturation Presence of previous crystals of the same material required Precipitation Batch crystallisation Continuous crystallisation after ter Horst et al., in Handbook of Crystal Growth, 2 nd Ed (2015)

3 Why is secondary nucleation important Two examples: Seeded batch crystallisation: often want to keep the crystal number constant so need to prevent primary or secondary nucleation therefore zero (or negligible) rate of secondary nucleation is required Continuous stirred tank crystallisation (MSMPR): secondary nucleation is typically required for steady supply of new crystals so rate of secondary nucleation needs to be controlled (known/modelled/predicted)

4 Control of crystal number and size Consider a batch crystallisation process where a certain amount of solution is brought to supersaturated state (say by cooling or adding antisolvent). A certain number of crystals is introduced through seeding or primary nucleation. Hofmann and Melches, in Crystallization (2013) Resulting particle size distribution is controlled by number of crystals: smaller number will result in larger final crystals (at given solid yield)

5 Secondary vs primary nucleation Secondary nucleation has been defined (Botsaris, 1976) as: nucleation which takes place only because of the prior presence of crystals of the material being crystallised (so may be another polymorph or chirality) So: secondary nucleation of a solid phase of a substance occurs due to presence of particle(s) of the same substance vs heterogeneous primary nucleation occurs due to presence of other interfaces Secondary nucleation can have variety of mechanisms

6 Nucleation: proposed classifications Beckmann, Crystallization (2013) Mullin, Crystallization, 4 th Ed (2001) Mersmann, Crystallization Technology Handbook, 2 nd Ed (2001) Agrawal and Paterson, Chem. Eng. Commun. 2015, 202, 698 Myerson, Handbook of Industrial Crystallization, 2 nd Ed (2002) Tung et al., Crystallization of Organic Compounds (2009)

7 Secondary nucleation: extensive literature, but still Garside et al., Origin and size distribution of secondary nuclei, AIChE J. 1979, 25, 57 Although secondary nucleation appears to be major source of nuclei in industrial crystallisation, little is known about the mechanism by which such nuclei are produced. Garside and Davey, Secondary contact nucleation: kinetics, growth and scale-up, Invited Review in Chem. Eng. Commun. 1980, 4, 393..some 35 year later. Cui and Myerson, Experimental evaluation of contact secondary nucleation mechanisms, Cryst. Growth Des. 2014, 14, 5152 Despite years of studies, the mechanism of contact secondary nucleation has not been resolved Coles and Threlfall, A perspective on a century of inert seeds in crystallisation, CrystEngComm 2014, 16, 4355 Agrawal and Paterson, Secondary nucleation: mechanisms and models, Chem. Eng. Commun. 2015, 202, 698. Threlfall and Coles, A perspective on the growth only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation, CrystEngComm 2016, 18, 369

8 Secondary nucleation scenarios One can consider following scenarios: Parent crystal present in stagnant solution (is any fluid ever stagnant?) Parent crystal subjected to fluid shear Parent crystal subjected to collision with impellers or vessel walls Parent crystal subjected to collision with others crystals

9 Solubility, metastability, nucleation threshold Primary and secondary metastable zone Threlfall and Coles, CrystEngComm 2016, 18, 369

10 Probing metastable region K 2 Cr 2 O 7 in water Isonicotinamide in ethanol after Janse and de Jong, On the width of the metastable zone, Trans. Inst. Chem. Eng. 1978, 56, 187 Secondary nucleation can be studied in the metastable zone, but interference from primary nucleation can be an issue Briuglia et al., in preparation

11 Quantification of secondary nucleation kinetics 1) Batch seeding with single or multiple crystals Counting numbers of newly formed particles (either total or as function of time) 2) Steady state stirred tank crystalliser (MSMPR) experiments: Measuring steady state crystal size distribution (CSD) and analysing number density data (assuming absence of primary nucleation and agglomeration and breakage) 3) Other arrangements (unsteady state/batch/plug flow): Measuring CSD and fitting with population balance models to estimate secondary nucleation kinetics (assuming certain functional expressions)

12 Primary and secondary nucleation kinetics measurements Clear solution Single Crystal Final Suspension Isonicotinamide in ethanol Primary Nucleation or Seeding Secondary Nucleation Isothermal primary nucleation kinetics measurement Primary nucleation rate: J Growth time: t g

13 Secondary nucleation kinetics: single crystal seeding Secondary nucleation rate (a.u.) Saturation temperature Seeding with single crystal Isothermal conditions reached Seed size (projected area/mm 2 ) Particle count Seeded Unseeded Secondary nucleation threshold and isothermal nucleation kinetics assessed using Crystalline platform

14 Steady state crystal size distribution in stirred tank crystalliser (MSMPR) Steady state number density distribution: n(l) = (B 0 /G) exp(- L / Gτ ) Measure number density distribution n(l) ln n(l 0 ) = ln(b 0 /G) Estimate: - nucleation rate B 0 (nuclei of size L 0 ) - linear crystal growth rate G Seeded systems: B 0 = N 0 /τ N 0 : number concentration of seeds in inlet stream τ : mean residence time L 0 after Davey and Garside, From molecules to crystallizers (2000)

15 Non-ideal steady state crystal size distributions: growth rate dispersion, size dependent growth Measured CSD often nonlinear: - growth rate dispersion - breeding of seeds in range of sizes (up to tens of µm) - size dependent growth (cf also inert seed phenomena) Garside and Jancic, Measurement and scale-up of secondary nucleation kinetics for the potash alum-water system, AIChE J. 1979, 25, 948 Inert seeds phenomena: Coles and Threlfall, CrystEngComm 2014, 16, 4355 Threlfall and Coles, CrystEngComm 2016, 18, 369

16 Initial breeding, attrition, fragmentation Initial breeding, attrition and fragmentation mechanisms can be seen as mechanical separation of preformed crystals (or their pieces) from larger crystals or aggregates/agglomerates. Due to collisions with impellers, vessel walls or with other crystals or due to fluid action on crystal (e.g., fluid shear or turbulent eddies) Can be also seem as crystal breakage or deaggregation/deagglomeration. Can be studied separately from crystal growth, i.e., in saturated solutions or non-solvents

17 Initial breeding Fine crystalline dust attached to surface of larger dry crystals is detached when seed crystals are suspended in solution and these detached fine crystals appear to be new nuclei This effect can be reduced/removed by washing seed crystals

18 Seed crystals & initial breeding SEM images showing size and surface of seed crystals prepared by three different methods: crystallized-sieved seed (a and b) milled-washed-sieved seed (c and d) milled-sieved seed (e and f ) K 2 Cr 2 O 7 in water ball mill, wash with isopropanol Aamir et al, Cryst Growth & Des 2010, 10, 4728

19 Initial breeding This experimental study examined factors affecting the number and characteristics of crystals produced by initial breeding in seeded batch crystallizers. The number of crystals formed was found to depend on the surface area of the seed crystals but not the supersaturation prevailing in the solution. This mechanism of secondary nucleation produced crystals in the order of 5 µm in size. Girolami and Rousseau: Initial breeding in seeded batch crystallizers Ind Eng Chem Process Des Dev 1986, 25, 66 Potassium alum (KAl(SO 4 ) 2 12H 2 O in water

20 Attrition Small pieces of larger crystals are broken off due to mechanical collisions (e.g., with impeller) and these small crystalline pieces appear to be new nuclei This effect can be influenced by suitably designing crystalliser vessel, agitation and suspension density

21 Attrition Potassium sulfate crystals suspended in methanol Ayazi Shamlou at el: Hydrodynamics of secondary nucleation in suspension crystallization, Chem Eng Sci 1990, 45, 1405

22 Ayazi Shamlou at el: Hydrodynamics of secondary nucleation in suspension crystallization, Chem Eng Sci 1990, 45, 1405 Potassium sulfate crystals suspended in methanol

23 Ayazi Shamlou at el: Hydrodynamics of secondary nucleation in suspension crystallization, Chem Eng Sci 1990, 45, 1405 The data indicate that, under operating conditions similar to those found in industrial crystallizers, secondary nuclei are produced by a particle attrition process consistent with a turbulent fluidinduced breeding mechanism having critical eddies in the viscous dissipation subrange of the turbulent energy spectrum.

24 Attrition Crystals falling on glass plate in evacuated tube Crystals suspended in agitated crystalliser Gahn et al., The effect of impact energy and the shape of crystals on their attrition rate, J. Cryst. Growth 1996, 166, Chianese et al., On the size distribution of fragments generated by crystal collisions, Chem. Eng. Commun. 1996, 146, 1 Gahn et al., Brittle fracture in crystallization processes. Part A. Attrition and abrasion of brittle solids Chem. Eng. Sci. 1999, 54, 1273 See chapter on attrition in Mersmann s handbook (2001)

25 Fragmentation Larger crystals are smashed into fragments due to mechanical collision (e.g., with magnetic stirring bar) and these crystalline fragments appear to be new nuclei This effect can be influenced by suitably designing crystalliser vessel, agitation and suspension density Kee and Rielly, Chem. Eng. Res. Des. 2004, 82, 1237 Measurement of particle impact frequencies and velocities on impeller blades in a mixing tank (thin coating of plasticine on the impeller blades to record craters formed by particle impacts) Reeves and Hill, Mechanisms influencing crystal breakage experiments in stirred vessels, Cryst. Growth Des. 2012, 12, 2748 (comparison of non-solvent and saturated solution experiments)

26 Key effects in mechanically induced attrition and breakage in stirred tanks Supersaturation Crystal concentration or mass Crystal mechanical properties Crystal size and shape Agitation/flow: - impeller rotation speed - impeller tip velocity - power input or energy dissipation rate - impeller geometry and mechanical properties - vessel geometry and flow patterns

27 Dendritic or needle breeding Very fast growth/ high supersaturation Dendritic/needle-like growth from surface of crystals Pieces of crystalline material easily broken off by fluid flow or mechanical action Succinonitrile dendrite growth image from Langer, Instabilities and pattern formation in crystal growth, Rev. Mod. Phys. 1980, 52, 1

28 Surface induced polymorphic transformation: β crystals of L-glutamic acid growing from α crystals Cashell et al., Secondary nucleation of the β-polymorph of L-glutamic acid on the surface of α-form crystals, Chem. Commun. 2003, 374 Ferrari and Davey, Solution-mediated transformation of α to β L-glutamic acid: rate enhancement due to secondary nucleation, Cryst. Growth Des. 2004, 4, 1061.

29 Attrition/breakage vs contact and shear nucleation van der Heijden et al, The secondary nucleation rate: a physical model, Chem Eng Sci 1994, 49, 3103 Kitamura and Hayashi, Ind Eng Chem Res 2016, 55, 1413

30 Contact secondary nucleation: crystal-wall contact Parent crystal Contacting rod Glass plate where parent crystal is slid Parent crystal Garside et al., Origin and size distribution of secondary nuclei, AIChE J. 1979, 25, 57 Shanks and Berglund, Contact nucleation from aqueous sucrose solutions, AIChE J. 1985, 31, 152

31 Contact secondary nucleation: quantitative evaluation Parent crystal Garside et al., Origin and size distribution of secondary nuclei, AIChE J. 1979, 25, 57

32 Continuous secondary nucleator Rousseau et al., Stability of nuclei generated by contact nucleation, AIChE J. 1975, 21, 1017 Tai et al., Contact nucleation of various crystal types, AIChE J. 1975, 21, 351 Wong et al., Contact secondary nucleation as a means of creating seeds for continuous tubular crystallizers, Cryst. Growth Des. 2013, 13, 2514

33 Statistical model for secondary nucleation rate Particle size distribution of seed crystals Diphenhydramine hydrochloride in isopropanol A response surface model was constructed by conducting a statistical design of experiment that models the nucleation rate as a function of contact force, area and frequency. Cui et al., Statistical design of experiment on contact secondary nucleation as a means of creating seed crystals for continuous tubular crystallizers, Org. Process Res. Dev. 2015, 19, 1101

34 Secondary nucleation mechanism: polymorphs γ-glycine crystal (1,0,1 plane) whether contact secondary nuclei originate from parent crystals via microattrition or from semiordered solute clusters at the interface of parent crystals. Cui and Myerson, Experimental evaluation of contact secondary nucleation mechanisms, Cryst. Growth Des. 2014, 14, 5152

35 Secondary nucleation of enantiomorphs Seeded nucleation of NaClO 3 enantiomorphs in non-agitated solution From Mullin, Crystallization (2000), after Denk and Botsaris, J. Cryst. Growth 1972, 13/14, 493

36 Fluid induced secondary nucleation: chiral systems Buhse et al., Chiral symmetry breaking in crystallization: The role of convection, Phys. Rev. Let. 2000, 84, 4405

37 Fluid flow induced secondary nucleation NaClO 3 ( seed crystal) sedimented in NaBrO 3 (supersaturated) solution Before After NaBrO 3 crystals of same chirality as NaClO 3 seed crystal No crystals observed immediately when seeded with NaBrO 3 crystals or in NaClO 3 solutions

38 Fluid flow induced secondary nucleation NaClO 3 seed crystal wetted by NaBrO 3 (S=1.2, 18ºC) solution

39 Secondary nucleation due to fluid shear Sung et al., Secondary nucleation of magnesium sulfate by fluid shear, AIChE J. 1973, 19, 957

40 Secondary nucleation due to fluid shear Seed crystal Couette cell Inner cylinder rotating Turbulent flow conditions Agitated for 30 s at given temperature then subcooled by 15ºC to grow nuclei Dendritic growth not present Wang et al., Secondary nucleation of citric acid due to fluid forces in a Couette flow crystallizer, AIChE J. 1981, 27, 312

41 Secondary nucleation due to fluid shear Wang et al., Secondary nucleation of citric acid due to fluid forces in a Couette flow crystallizer, AIChE J. 1981, 27, 312

42 Secondary nucleation: molecular simulations of LJ crystals Figure 1. Snapshots from molecular dynamics simulations of a crystal slab (representing the seed crystal) immersed in a supersaturated solution of solute, illustrating the three supersaturation regimes: crystal growth, surface-induced nucleation of clusters, and spontaneous nucleation in solution. Anwar et al., Angew. Chem. Int. Ed. 2015, 54, Figure 2. Snapshots from a molecular dynamics simulation trajectory showing the stepwise formation of crystalline structures on the surface of the seed crystal for the moderately supersaturated system (Lennard Jones solute solvent affinity parameter ε=3.0 kj/mol). Anwar et al., Angew. Chem. Int. Ed. 2015, 54, 14681

43 Secondary nucleation threshold Srisa-nga et al., The Secondary Nucleation Threshold and Crystal Growth of α-glucose Monohydrate in Aqueous Solution, Cryst. Growth Des. 2006, 6, 795

44 Secondary nucleation in stirred tanks: dependence on crystal size MgSO 4 7H 2 O in water Bauer et al., Influence of crystal size on the rate of contact nucleation in strirred tank crystallizers, AIChE J. 1974, 20, 653

45 Secondary nucleation kinetics in stirred tanks Yokota et al., Scale up effect of the rate of contact nucleation caused by collisions of crystals with an impeller, Chem. Eng. Sci. 1999, 54,3831