(57d) Relating Chord-Length and Size Distributions: Applications in the Batch Crystallization of Paracetamol

Control of crystal size distributions (CSD) can insure that downstream processing and product quality meet expectations. One of the most difficult aspects of implementing such control is the limited existing capability to monitor CSD in an unambiguous manner. Moreover, the ability to observe on-line the evolution of the CSD can constitute a major asset in understanding crystallizer operation and the phenomena that influence product quality.

The development of new technologies, such as focused beam reflectance measurement (FBRM), provides a methodology for on-line monitoring of a representation of the crystal population in either batch or continuous crystallization systems. The FBRM technology is based on laser light scattering. If properly installed it allows on-line determination of the chord length distribution (CLD), which is statistically related to the CSD and strongly depends on the geometry of the crystal. Unfortunately, the CLD does not give direct information on the CSD. Therefore, a model was established to relate both distributions and thus enable computation of the CSD from a measured CLD. The model essentially is based on the simulation of a conversion matrix regrouping in a defined order the probable CLDs of crystals of a given size and shape.

In the pharmaceutical and specialty chemical industries, batch crystallization is used widely in the production of high-value added species. We will focus here on applying the developed model to batch cooling crystallization of paracetamol from ethanol solutions. Paracetamol (also known as acetaminophen) is a common substance, mainly used as an analgesic and antipyretic drug, on which large amounts of data exist. It is particularly useful in the present study because of its shape; it crystallizes in octahedral shapes, which are easily described mathematically. The accuracy of CSD predictions from measured CLD data was examined by comparing such values to experimental sieve measurements of CSD. Agreement was quite good, and the presentation will illustrate how the model can be used in a number of practical applications.