453501 Evidence of Crystal Nuclei Breeding in Laboratory Scale Seeded Batch Isothermal Crystallisation Experiments

Tuesday, November 15, 2016: 9:10 AM
Bay View (Hotel Nikko San Francisco)
Brian de Souza1, Giuseppe Cogoni1, Rory Tyrrell2 and P.J. Frawley3, (1)Mechanical, Aeronautical and Biomedical Engineering, SSPC, University of Limerick, Limerick, Ireland, (2)MABE, University of Limerick, Limerick, Ireland, (3)Mechanical, Aeronautical and Bio-medical Engineering, SSPC, MSSI, University of Limerick, limerick, Ireland

Experimental investigations of the batch seeded crystallisation of paracetamol in 2-propanol were carried at 200, 300 &375 RPM agitation rates, using a large seed size (355-500 µm) and a low level of initial supersaturation (S0=1.2) in a laboratory scale reactor.  Such experiments are normally conducted for the indirect measurement of crystal growth, contingent on the assumption of negligible nucleation, agglomeration and breakage.  In the present work a copious increase in crystals nuclei was noted shortly following seed addition.  The formation of substantial numbers of new nuclei was substantiated through FBRM, laser diffraction and SEM.  Secondary nucleation was proposed as the origin of the new crystals and a Secondary Nucleation Threshold (SNT) of between 1.09-1.11 determined, beyond which crystal growth only was apparent.  A study was undertaken to investigate the origin of secondary nucleation.  Crystal nuclei breeding, as a mechanism of secondary nucleation, has being theorised for many years, however it is only very recently that definitive molecular dynamics simulations have provided mechanistic insight as to its action.  The mechanically driven attrition and breakage mechanism of secondary nucleation remains prominent in literature.  Stirred vessel experiments were conducted using paracetamol seed crystals suspended in a non-solvent indicated.  Despite three hours of continuous agitation, no significant change in particle number or size was detected.  Only after a threshold of four hours were significant crystal fatigue and fragmentation evident.  Shadowgraphy investigations of crystal jet wall impingement revealed the squeeze film as a key protective element in preventing crystal attrition and breakage.  A low temperature (283.15 K) crystallisation was conducted which indicated a significant temperature dependency, entirely inconsistent with the attrition and breakage mechanism of secondary nucleation.  It was shown that through the use of smaller seed crystals (125-250 µm), a high agitation rate and elevated solution temperature that the rate of secondary nucleation could be enhanced thereby creating the potential for confounding rapid secondary nucleation with growth.  The current work elucidates the potential impact of cluster breeding in laboratory scale crystallisations and furthermore, provides additional experimental support for the crystal breeding mechanism of secondary nucleation.

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