2022年针状晶体生长机理 .pdf
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1、Journalof CrystalGrowth310 (2008) 110115Crystallizationmechanisms of acicular crystalsFranc -ois Puela, Elodie Verduranda, Pascal Taulelleb, Christine Bebona, DidierColsona,Jean-Paul Kleina, Stephane Veeslerb,?aLAGEP,UMRCNRS5007, Universite Lyon 1, CPE Lyon,Ba ?t. 308G, 43 Bd du 11 novembre 1918, F-
2、69622 VilleurbanneCedex, FrancebCentre de Recherche en Matiere Condense e et Nanosciences (CRMCN)1CNRS,Campus de Luminy,Case 913, F-13288 MarseilleCedex 09, FranceReceived 10 September 2007; accepted 3 October2007Communicatedby K. SatoAvailableonline 9 October2007AbstractIn this contribution,we pres
3、ent an experimental investigationof the growth of four different organic molecules produced at industrialscale with a view to understand the crystallizationmechanism of acicular or needle-like crystals. For all organic crystals studied in thisarticle, layer-by-layer growth of the lateral facesis ver
4、y slow and clear, assoon as the supersaturation is high enough, there is competitionbetween growthand surface-activatedsecondary nucleation.This gives rise to pseudo-twinnedcrystals composed of several needleindividualsaligned along a crystallographicaxis; this is explained by regular over- and inte
5、r-growthsas in the case of twinning.Andwhen supersaturationis even higher, nucleation is fast and random.In an industrialcontinuous crystallization,the rapid growth of needle-like crystals is to be avoided as it leads to fragile crystals orneedles, whichcan be partlybrokenortotallydetached fromthe p
6、arentcrystalsespecially alongstructuralanisotropicaxiscorrespondingto weaker chemical bonds, thus leading to slower growing faces. When an activated mechanism is involved such as asecondary surface nucleation,it is no longer possible to obtaina steady state. Therefore,the crystal number, size and ha
7、bit varysigni?cantlywithtime, leading to troubles in the downstreamprocessing operationsand to modi?cationsof the ?nal solid-speci?cproperties.These results provide valuable informationon the unique crystallizationmechanisms of acicular crystals, and show that it is importantto know these threshold
8、and criticalvalues when runninga crystallizer in order to obtain easy-to-handle crystals.r2007 Elsevier B.V. All rights reserved.PACS:81.10.Aj;81.10.Dn;78.30.JwKeywords: A1. Crystalmorphology;A2. Growthfromsolutions;B1. Organiccompounds1. IntroductionManyorganicmolecules exhibitanisotropicstructural
9、propertiesin theircrystallineform,whichgives rise toacicularorneedle-likecrystals.Inthechemicalandpharmaceuticalindustry,crystallizationfromsolutionisused as a separationtechnique,and this crystalhabitisusuallynot desirable,especially when the internallength-to-widthratiois high,as itwillleadtoprobl
10、emsindownstreamprocesses (?ltration,drying, storage, handling,etc.).A better understandingof the mechanisms of nucleationand growth of these needle-like crystals will therefore leadtobettercontrolofcrystallizationprocesses.Intheliterature,papers on molecularmodelingof these needle-likecrystals1 3 su
11、ggest thatin the case ofneedle-likecrystals,thereisnoslow-growingfaceintheneedledirection.Practicalaspects have been also studied forafew years now in our differentresearch teams 4 6 .Inthiscontribution,wepresentanexperimentalinvestigationofthegrowthoffourdifferentorganicmoleculesproducedat industri
12、alscale witha viewtounderstandthecrystallizationmechanismofacicularARTICLE IN PRESS - see frontmatter r2007 Elsevier B.V. All rightsreserved.doi: 10.1016/j.jcrysgro.2007.10.006?Correspondingauthor.Tel.: +336 6292 2866; fax: +334 9141 8916.E-mailaddress: veeslercrmcn.univ-mrs.fr(S. Veesler).1Laborato
13、ryassociated to the UniversitiesAix-MarseilleIIand III.名师资料总结 - - -精品资料欢迎下载 - - - - - - - - - - - - - - - - - - 名师精心整理 - - - - - - - 第 1 页,共 6 页 - - - - - - - - - crystals from the molecularto the macroscopicscales. Forall organiccrystalsstudiedin thisarticle,layer-by-layergrowthof the lateral faces
14、 is very slow and clearly, as soonas supersaturationis highenough,thereis competitionbetween growthand activated secondary nucleation.Theseinvestigationsshow that crystals are agglomeratedwith thesame crystallographicorientationfor the individualcon-stituents,as observedbyopticalmicroscopy,scanninge
15、lectronmicroscope(SEM)and atomicforce microscopy(AFM);this is explained by regular over- and inter-growthsas in the case of twinning.Andwhen supersaturationiseven higher, nucleationis fast and random.These resultsprovidevaluable informationon the unique crystallizationmechanismsofacicularcrystals,an
16、dshowthatitisimportanttoknowthese thresholdandcriticalvalueswhenrunninga crystallizerin orderto obtaineasy-to-handle crystals.2. Materialsand methods2.1. MaterialsThe four organic molecules studied were:(i) Irbesartan(C25H28N6O),anactivepharmaceuticalingredientcrystallizedin2-propanolandused bySano?
17、-Aventisin the treatmentof hypertension;(ii) Product2 (for the sake of con?dentiality),an organicmoleculeexhibitinganalkylcycle withone polarchemicalgroup:thismoleculecrystallizesinitsindustrialsolvent;(iii)Hydroquinone(C6H6O2), which crystallizes in water inthe presence of an additiveused at indust
18、rialscale tospeci?callyreduce growthalong the length axis of theneedle;(iv) Product4 (forthe sake of con?dentiality)knowntoexhibitonlyneedle-likehabitwhateverthesolventused.Structuraldata for the ?rst three molecules are presentedin Table 1.2.2. Solid CharacterizationCrystalswere observed undera (SE
19、M;JEOL6320F).SEMphotographsclearlyshowtheneedle-likecrystalhabitforthe foursystems studied(Fig.1). CrystalsofIrbesartanphase A were also observed by AFMusing aDigitalNanoscopeIIIatomic force microscopeequippedwitha 12mm scanner.Images were collectedin tappingmode using oxide-sharpenedSi3N4cantilever
20、tips (nano-probeTM).2.3. CrystalpreparationIrbesartanandProduct4crystalsweregrowninquiescentsolutions(2 mL)atknownconcentrations,underopticalmicroscope(Nikon,Diaphot),atgiventemperatures,usingtheexperimentalsetuppreviouslydescribed 7.Product 2 and hydroquinonecrystals were obtainedfromisothermal cry
21、stallizationin 2.5 L stirred vesselsin semi-batchand continuousoperations,respectively. Experimentalpro-cedures can be foundin the followingreferences 5,6,8.The supersaturationis de?ned as b= C/Ce, with C and Cearetheconcentrationandsolubilityoftheorganicmolecule.3. Results and discussionAs shown in
22、 Fig. 1, all the crystals present a needle-likehabit, whichis due to a strong structuralanisotropyalongthe z-axis for Irbesartanand hydroquinone,and x-axis forProduct2 (see Table 1). This was con?rmedby molecularmodelingfor Irbesartan4 and Product2 9. Product4structurehas not yet been determined.ART
23、ICLE IN PRESSTable 1StructuraldataIrbesartanphase AaProduct2Hydroquinonephase aaa (A )37.094.92238.46b (A )37.0915.71438.46c (A )9.658.1745.65a (1)909090b (1)90104.690g (1)12090120aInterestingly,Irbesartanphase A and hydroquinonephase a have thesame space groupR-3.Fig.1. Needle-likecrystalsobservedb
24、y SEM:(a) Irbesartanphase A,(b) Product2, (c) hydroquinonephase a and (d) Product4.F. Puel et al. / Journal of CrystalGrowth 310 (2008)110115111名师资料总结 - - -精品资料欢迎下载 - - - - - - - - - - - - - - - - - - 名师精心整理 - - - - - - - 第 2 页,共 6 页 - - - - - - - - - 3.1. Crystallizationof Irbesartanin stagnant con
25、ditionsThe experimentsshow thatin all the temperatureandsupersaturationranges,220 1C and310,respectively,crystals obtained (Fig. 2a, c and d) have a needle-like habit,composedby crystallineagglomerates.2Moreover,whensupersaturationistoolow,topfacesdonotgrow.Supersaturationmust exceed a thresholdvalu
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