University of Limerick
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Impact of fluid shear on particle size distribution of batch crystallization processes in stirred vessels

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posted on 2023-01-20, 08:55 authored by Brian Hogan
Crystallization is a puriification process during which molecules of a crystal compound bond together arranging themselves in a compound specific orderly lattice structure in which foreign molecules known as impurities do not precisely fit the structural pattern of the growing crystal. Thus their inclusion in the crystal lattice while not impos sible is certainly difficult resulting in a largely pure crystal. Crystalization is a key process in the pharmaceutical industry as it is used to produce the active pharmaceutical ingredient (API) that is absor bed in a patient's body to deliver the desired medical effect, thus high product purity is paramount. During crystallization processes undesirable quantities of nanocrystals are commonly generated causing challenges in downstream processing such as clogging of fillters. The lack of complete understanding of the cause of fines prevents the achievement of consistent particle size distributions (PSDs). In pharmaceutical laboratory experiments increased rotational speeds have brought about large increases in particle numbers with much of the product material lost to fines. The increased particles numbers are assumed to be caused by increased shearing of nuclei off the surface of seed particles. This thesis examines the change of phase resolved fluid velocity and shear stress as a result of rotational speed and impeller type and examines the infuence of baffles. An experimental set-up was designed to best replicate the mixing vessel of a Labmax where the initial crystallization experiments of Paracetamol in IPA yielding large particle numbers were carried out. Particle Image Velocimetry (PIV) was used to measure particle ow velocities from which turbulent shear stresses are calculated. Finally, the direct influence of impeller type on particle size distribution (PSD) was examined in cooling batch crystallization experiments again of Paracetamol in IPA in an Optimax using a mixing vessel of the same size and dimensions of both a Labmax and the mixing vessel used in PIV experiments. Results conclusively show an increase of particle count with increased shear stress as the impeller types that generate the highest shear stresses also produce the highest particle counts. Particle size distributions for all impeller types also show lower mean values for higher shear impellers but also a larger number of finnes and a lower number of large particles. Knowledge of the effects of shear stresses in crystallization processes permit better control over final PSDs whether through impeller type selection, rotational speed selected, the use of baffles or a combination of all. Based on extensive experimental data an equation to predict turbulent shear stress in stirred vessels is pro- posed to prevent the necessity of complex measurement techniques for newly designed crystallization experiments.



  • Doctoral

First supervisor

Frawley, Patrick J.



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Also affiliated with

  • Synthesis and Solid State Pharmaceutical Centre

Department or School

  • School of Engineering

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