Efficient processing of particulate products across various manufacturing steps requires that particles possess desired attributes such as size and shape. Controlling the particle production process to obtain required attributes will be greatly facilitated using robust algorithms providing the size and shape information of the particles from in situ measurements. However, obtaining particle size and shape information in situ during manufacturing has been a big challenge. This is because the problem of estimating particle size and shape (aspect ratio) from signals provided by in-line measuring tools is often ill posed, and therefore it calls for appropriate constraints to be imposed on the problem. One way to constrain uncertainty in estimation of particle size and shape from in-line measurements is to combine data from different measurements such as chord length distribution (CLD) and imaging. This paper presents two different methods for combining imaging and CLD data obtained with in-line tools in order to get reliable estimates of particle size distribution and aspect ratio, where the imaging data is used to constrain the search space for an aspect ratio from the CLD data

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Besides size and polymorphic form, crystal shape takes a central role in engineering advanced solid materials for the pharmaceutical and chemical industries. This work demonstrates how multiple cycles of growth and dissolution can manipulate the habit of an acetylsalicylic acid crystal population. Considerable changes of the crystal habit could be achieved within minutes due to rapid cycling, i.e., up to 25 cycles within <10 min. The required fast heating and cooling rates were facilitated using a tubular reactor design allowing for superior temperature control. The face-specific interactions between solvent and the crystals’ surface result in face-specific growth and dissolution rates and hence alterations of the final shape of the crystals in solution. Accurate quantification of the crystal shapes was essential for this work, but is everything except simple. A commercial size and shape analyzer had to be adapted to achieve the required accuracy. Online size, and most important shape, analysis was achieved using an automated microscope equipped with a flow-through cell, in combination with a dedicated image analysis routine for particle tracking and shape analysis. Due to the implementation of this analyzer, capable of obtaining statistics on the crystals’ shape while still in solution (no sampling and manipulation required), the dynamic behavior of the size shape distribution could be studied. This enabled a detailed analysis of the solvent’s effect on the change in crystal habit.