Abstract
A novel shadowgraphic inline probe to measure crystal size distributions (CSD), based on acquired greyscale images, is evaluated in terms of elevated temperatures and fragile crystals, and compared to well-established, alternative online and offline measurement techniques, i.e., sieving analysis and online microscopy. Additionally, the operation limits, with respect to temperature, supersaturation, suspension, and optical density, are investigated. Two different substance systems, potassium dihydrogen phosphate (prisms) and thiamine hydrochloride (needles), are crystallized for this purpose at 25 L scale. Crystal phases of the well-known KH2PO4/H2O system are measured continuously by the inline probe and in a bypass by the online microscope during cooling crystallizations. Both measurement techniques show similar results with respect to the crystal size distribution, except for higher temperatures, where the bypass variant tends to fail due to blockage. Thiamine hydrochloride, a substance forming long and fragile needles in aqueous solutions, is solidified with an anti-solvent crystallization with ethanol. The novel inline probe could identify a new field of application for image-based crystal size distribution measurements, with respect to difficult particle shapes (needles) and elevated temperatures, which cannot be evaluated with common techniques.
Highlights
Crystallization is widely applied in agricultural, pharmaceutical, or chemical industry, with an enormous variety of duties and products
Control of the crystal size and solid-state form is one important challenge that spreads over all fields of industrial crystallization [4]
Thebypass bypass online microscope inserted at top the of top the reactor, directly the shadowgraphic probe to ensure that the withdrawn suspension was similar
Summary
Crystallization is widely applied in agricultural, pharmaceutical, or chemical industry, with an enormous variety of duties and products. While for fine chemicals or active pharmaceutical ingredients (API) the solid-state form is commonly of major interest, a certain crystal size distribution (CSD) and crystal shape is usually demanded. Any of these particular properties affect the product functionality [1], as well as other processes in the downstream procedure (filtration, drying, etc.) [2,3]. A defined seeding strategy, combined with a controlled cooling policy, are utilized to meet the rigorous product specifications This is the most common approach for process development and commercial manufacturing, but it has various disadvantages. The results of three different techniques for the measurement of CSD are compared with the example of two substance systems in a wide range of operation conditions
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