Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building ef...Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building efficient manufacturing processes. In this paper, we review recent developments in crystal engineering and crystallization process design and control in the pharmaceutical industry. We systematically summarize recent methods for understanding and developing new types of crystals such as co-crystals, polymorphs, and solvates, and include several milestones such as the launch of the first co-crystal drug, Entresto （No- vartis）, and the continuous manufacture of Orkambi （Vertex）. Conventional batch and continuous processes, which are becoming increasingly mature, are being coupled with various control strategies and the recently developed crystallizers are thus adapting to the needs of the pharmaceutical industry. The development of crystallization process design and control has led to the appearance of several new and innovative crystal- lizer geometries for continuous operation and improved performance. This paper also reviews major recent orogress in the area of process analytical technology.展开更多
A new technique for ice slurry production was explored. Multiple small water-drops were formed in another immiscible chilled liquid by a single-nozzled atomizer and frozen in the fluidized bed by direct contact heat t...A new technique for ice slurry production was explored. Multiple small water-drops were formed in another immiscible chilled liquid by a single-nozzled atomizer and frozen in the fluidized bed by direct contact heat transfer. Experiments were conducted to investigate the dynamic behaviors of the ice crystal making system. The results demonstrate that the ice crystals could be produced continuously and stably in the vertical bed with the circulating coolant of initial temperature below -5℃. The size distribution of the ice crystals appears non-uniform, but is more similar and more uniform at lower oil flow rate. The mean ice crystal size rests seriously with the jet velocity and the oil flow rate. It decreases with decreasing the oil flow rate, and reaches the maximum at an intermediate jet velocity at about 16.5 m.s y. The ice crystal size is also closely related to the phenomenon of drop-coalescing, which can be alleviated considerably by reducing the flow rate or lowering the temperature of the carrier oil. However, optimization of liquid-liquid atomization is a more effective approach to produce fine ice crystals of desired size.展开更多
Recent research has demonstrated that on-line video imaging is a very promising technique for monitoring crystallization processes. The bottleneck in applying the technique for real-time closed-loop control is conside...Recent research has demonstrated that on-line video imaging is a very promising technique for monitoring crystallization processes. The bottleneck in applying the technique for real-time closed-loop control is considered as image analysis that needs to be robust, fast and able to handle varied image qualities due to temporal variations of operating conditions such as mixing and solid concentrations. Image analysis at highsolid concentrations turns out to be extremely challenging because crystals tend to overlap or attach to each other and the boundaries between the crystals are usually ambiguous. This paper presents an image segmentation algorithm that can effectively deal with images taken at high-solid concentrations. The method segments crystals attached to each other along the mostly related concave points on the contours of crystal blocks. The detailed procedure is introduced with application to crystallization of L-glutamic acid in a hot-stage reactor.展开更多
文摘Crystallization is one of the oldest separation and purification unit operations, and has recently contributed to significant improvements in producing higher-value products with specific properties and in building efficient manufacturing processes. In this paper, we review recent developments in crystal engineering and crystallization process design and control in the pharmaceutical industry. We systematically summarize recent methods for understanding and developing new types of crystals such as co-crystals, polymorphs, and solvates, and include several milestones such as the launch of the first co-crystal drug, Entresto （No- vartis）, and the continuous manufacture of Orkambi （Vertex）. Conventional batch and continuous processes, which are becoming increasingly mature, are being coupled with various control strategies and the recently developed crystallizers are thus adapting to the needs of the pharmaceutical industry. The development of crystallization process design and control has led to the appearance of several new and innovative crystal- lizer geometries for continuous operation and improved performance. This paper also reviews major recent orogress in the area of process analytical technology.
基金the Specialized Research Fund for the Doctoral Program of Higher Education of China(20060286034)
文摘A new technique for ice slurry production was explored. Multiple small water-drops were formed in another immiscible chilled liquid by a single-nozzled atomizer and frozen in the fluidized bed by direct contact heat transfer. Experiments were conducted to investigate the dynamic behaviors of the ice crystal making system. The results demonstrate that the ice crystals could be produced continuously and stably in the vertical bed with the circulating coolant of initial temperature below -5℃. The size distribution of the ice crystals appears non-uniform, but is more similar and more uniform at lower oil flow rate. The mean ice crystal size rests seriously with the jet velocity and the oil flow rate. It decreases with decreasing the oil flow rate, and reaches the maximum at an intermediate jet velocity at about 16.5 m.s y. The ice crystal size is also closely related to the phenomenon of drop-coalescing, which can be alleviated considerably by reducing the flow rate or lowering the temperature of the carrier oil. However, optimization of liquid-liquid atomization is a more effective approach to produce fine ice crystals of desired size.
文摘Recent research has demonstrated that on-line video imaging is a very promising technique for monitoring crystallization processes. The bottleneck in applying the technique for real-time closed-loop control is considered as image analysis that needs to be robust, fast and able to handle varied image qualities due to temporal variations of operating conditions such as mixing and solid concentrations. Image analysis at highsolid concentrations turns out to be extremely challenging because crystals tend to overlap or attach to each other and the boundaries between the crystals are usually ambiguous. This paper presents an image segmentation algorithm that can effectively deal with images taken at high-solid concentrations. The method segments crystals attached to each other along the mostly related concave points on the contours of crystal blocks. The detailed procedure is introduced with application to crystallization of L-glutamic acid in a hot-stage reactor.
