(523e) Investigations into the Use of Ultrasounds for Seed Generation for Continuous Cooling Crystallization Process in an Oscillatory Flow Baffled Crystallizer
AIChE Annual Meeting
2016
2016 AIChE Annual Meeting
Separations Division
Crystallization of Pharmaceutical and Biological Molecules II
Wednesday, November 16, 2016 - 1:55pm to 2:15pm
Investigations into the use of Ultrasound for Seed Generation for Continuous Cooling Crystallization Process in an Oscillatory flow Baffled Crystallizer
One of the challenges associated with tubular crystallizers in general is the high risk of scaling and uncontrolled nucleation due to the large surface area they offer. This poor control over nucleation leads to undesired product attributes which is detrimental for the production process. Oscillatory flow baffled crystallizer (OFBC) is a type of tubular crystallizer which offers the opportunity to manipulate and control the mixing conditions by controlling the amplitude and frequency of the flow oscillations. The control over mixing coupled with high heat transfer area offered by the (OFBC) also allows for better control of the process temperature and hence the super-saturation in the crystallizer, which is promising for controlling nucleation. Furthermore, the very low operating flowrates can be realized as the mixing in the OFBC is independent of the process flowrate. Thus, leading to large residence times in the comparatively compact set-up, when compared to a crystallizer with a simple tubular geometry. However, there is still a lack of understanding in terms of effect of local turbulence in the crystallizer on the nucleation and growth kinetics in a crystallization process. There have been concerns regarding the plugging and scaling of the crystallizers, possibly an influence of the large surface area. Additionally, introduction of seeds in the system, especially at low flowrates, has been challenging and has called for novel feed methods.
Since continuous operation carried out in a single or multiple well-mixed vessels connected in series leads to a broad residence time distribution in the crystallizer and hence results in poor process control, the use of such an infrastructure to generate seeds for feeding into the OFBC seems to be sub-optimal. Therefore we aim at the use of an external field in the form of ultrasound to gain on control of nucleation in a continuous flow set-up, if not to apply directly in the OFBC set-up.
Application of ultrasound (US) has been demonstrated to affect the crystallization process by reducing the induction time, promoting nucleation at relative low supersaturation levels. In this study we investigate the use of US for the continuous generation of small seed crystals in the feed stream of a continuous OFBC crystallizer. Two different reactors will be tested in their efficiency to generate the seed crystals, a tubular flow crystallizer surrounded by piezo electric element which induces ultrasound directly inside the tube and a flow cell in which an ultrasound horn is in direct contact with the flowing supersaturated solution. The number of nuclei entering the OFBC is monitored as well as the control to maintain growth only conditions in the crystallizer. The approach is aimed at the generation of a well-defined feed stream containing small seed crystals at a concentration that can suppress the undesirable (secondary) nucleation in the OFBC, yielding product crystals with a high quality, i.e mono modal with a narrow size distribution.
One of the challenges associated with tubular crystallizers in general is the high risk of scaling and uncontrolled nucleation due to the large surface area they offer. This poor control over nucleation leads to undesired product attributes which is detrimental for the production process. Oscillatory flow baffled crystallizer (OFBC) is a type of tubular crystallizer which offers the opportunity to manipulate and control the mixing conditions by controlling the amplitude and frequency of the flow oscillations. The control over mixing coupled with high heat transfer area offered by the (OFBC) also allows for better control of the process temperature and hence the super-saturation in the crystallizer, which is promising for controlling nucleation. Furthermore, the very low operating flowrates can be realized as the mixing in the OFBC is independent of the process flowrate. Thus, leading to large residence times in the comparatively compact set-up, when compared to a crystallizer with a simple tubular geometry. However, there is still a lack of understanding in terms of effect of local turbulence in the crystallizer on the nucleation and growth kinetics in a crystallization process. There have been concerns regarding the plugging and scaling of the crystallizers, possibly an influence of the large surface area. Additionally, introduction of seeds in the system, especially at low flowrates, has been challenging and has called for novel feed methods.
Since continuous operation carried out in a single or multiple well-mixed vessels connected in series leads to a broad residence time distribution in the crystallizer and hence results in poor process control, the use of such an infrastructure to generate seeds for feeding into the OFBC seems to be sub-optimal. Therefore we aim at the use of an external field in the form of ultrasound to gain on control of nucleation in a continuous flow set-up, if not to apply directly in the OFBC set-up.
Application of ultrasound (US) has been demonstrated to affect the crystallization process by reducing the induction time, promoting nucleation at relative low supersaturation levels. In this study we investigate the use of US for the continuous generation of small seed crystals in the feed stream of a continuous OFBC crystallizer. Two different reactors will be tested in their efficiency to generate the seed crystals, a tubular flow crystallizer surrounded by piezo electric element which induces ultrasound directly inside the tube and a flow cell in which an ultrasound horn is in direct contact with the flowing supersaturated solution. The number of nuclei entering the OFBC is monitored as well as the control to maintain growth only conditions in the crystallizer. The approach is aimed at the generation of a well-defined feed stream containing small seed crystals at a concentration that can suppress the undesirable (secondary) nucleation in the OFBC, yielding product crystals with a high quality, i.e mono modal with a narrow size distribution.