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The chemical industry has witnessed many important developments during past decades largely enabled by process intensification techniques. Some of them are already proven at commercial scale (e.g. reactive distillation) while others (e.g. ultrasound‐assisted extraction/crystallization/reaction) are on their way to becoming the next‐generation technologies. This article focuses on the advances of ultrasound (US)‐assisted technologies that could lead in the near future to significant improvements in commercial activities. The aim is to provide an authoritative discussion on US‐assisted technologies that are currently emerging from the research environment into the chemical industry, as well as give an overview of the current state‐of‐the‐art applications of US in chemical processing (e.g. enzymatic reactive distillation, crystallization of API). Sufficient information is included to allow the assessment of US‐assisted technologies and the challenges for implementation, as well as their potential for commercial applications. © 2017 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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The surface-induced melting of the close-packed (100) face of the anisotropic molecular crystal caprolactam has been studied using x-ray reflectivity. A thin-to-thick film prewetting transition is observed at about 13 K below the bulk melting point. Only above this transition does the thickness of the quasiliquid layer increase continuously with temperature. We speculate that initially the surface melting proceeds via layering transitions. PACS numbers: 64.70.Dv, 68.35.Rh, 68.45.GdThe experimental observation of a quasiliquid film wetting the solid-vapor interface below the melting temperature TM [1-5] has confirmed the old idea that the surface initiates the melting of a solid. Theoretically surface melting can be regarded as the wetting of the solid by the melt [5,6] and can result in either the quasiliquid film thickness remaining finite (incomplete wetting) or diverging (complete wetting) as the temperature approaches TM-In the latter case the divergence is governed by the range of the dominant interactions in the system. While long-range van der Waals interactions result in the thickness increasing as {TM ~ T)

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Batch cooling crystallization is a commonly used separation and purification step in the pharmaceutical industry. Various properties of the crystalline product from a batch crystallizer can have a strong impact on the efficiency of downstream processes such as filtration and drying, on the formulation process and on the dissolution behaviour of the drug. Development of the crystallization processes presents a major challenge in the process development of an active pharmaceutical ingredient (API). Therefore, it is beneficial to develop a rapid crystallization process development strategy to industrial scale. In this paper we present a strategy for rapid process development and apply this strategy for androsta-1,4-diene-3,17-dione, cyclic 17-(2,2-dimethyltrimethylene acetal), a pharmaceutical intermediate produced by Merck Sharp and Dohme. The major advantages of the strategy are that there is no requirement of the crystallizer design modification, the calibration of the process analytical technology (PAT) tools can be performed at industrial scale, and the determination of the operating window can be done directly at the industrial scale. This strategy allows for process optimization directly at the industrial scale, thus eliminating the need for time-intensive scale-dependent study. The implementation of this strategy at industrial scale was performed with the help of PAT tools arranged in a unique skid-based configuration. The skid which contains both the concentration sensors and the crystal size distribution (CSD) sensors can be connected to the existing crystallizers, thereby avoiding the time and cost-intensive modifications in the crystallizer design. The modular nature of the skid offers opportunities to choose the PAT tools which complement the solute–solvent model system. The skid makes it possible to gather the relevant information concerning the thermodynamics and kinetics of the model system in situ during the crystallization runs at the industrial scale. A strategy for process development based on a sensor skid is beneficial for the industry as it is intrinsically rapid and can be combined with the development of control strategies which lead to consistent product quality.

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