Scaling Up and Controlling Crystallization
Crystallization is a key pharmaceutical manufacturing operation. While the target is always to grow the desired crystals within a narrow size distribution, the nature of the crystallization process can make it difficult to achieve this level of control. One particular challenge is scaling up production to achieve the ideal particle size (which influences the final drug’s performance in the patient) and the ideal crystalline form (which can drastically affect biological performance).
Achieving perfect crystals involves perfect mixing and the control of concentration and temperature, this isn’t easy. A key to achieving ideal crystals is the ability to measure the formation of crystals at each stage of manufacture. One popular tool for keeping tabs on crystallization is Focused Beam Reflectance Measurement (FBRM): in this process, laser light hits tiny crystals as they grow and is reflected and measured. One limitation of FBRM is that it only notices particles above a certain size and so does not detect the onset of crystallization.
An alternative technology – Electrical Resistance Tomography (ERT) – offers some advantages. Developed by Manchester, U.K.-based Industrial Tomography Systems, it detects changes in conductivity and ion concentrations, both of which fall during crystallization. Thus, ERT can detect the onset of crystallization.
Gathering Data From the Entire Vessel
The technology can provide data throughout the vessel rather than at a specific point. For example, when electrodes are arranged around the circumference of the vessel – in Figure 1 there are eight planes with 16 electrodes per plane – ERT can monitor conductivity at more than 200 points at 20 to 40 times a second. At this speed, it effectively builds a clear real-time picture of mixing patterns and ion concentrations throughout the vessel.
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