The continuous‐flow production of active pharmaceutical ingredients is a spreading applicative research field. Process simulation tools are effective means for in silico process design, but care is needed. A paradigmatic example is the synthesis of ibuprofen. First, the most appropriate thermodynamic models must be selected. The rich databases now available to collect thermodynamic properties are often insufficient because unconventional molecules are usually part of the recipe or found as intermediates or products. Furthermore, in some reaction steps ionic properties may be needed rather than those of the neutral molecules. All these points need a careful optimization of the methods for the estimation of the properties, with possible huge discrepancies of the results.

中文翻译：

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布洛芬生产连续流工艺设计中的工艺建模问题

活性药物成分的连续流生产是一个广泛的应用研究领域。流程模拟工具是进行计算机流程设计的有效手段，但需要小心。一个典型的例子是布洛芬的合成。首先，必须选择最合适的热力学模型。由于非常规分子通常是配方的一部分或作为中间体或产品存在，因此现在可用于收集热力学性质的丰富数据库常常不足。此外，在某些反应步骤中，可能需要离子特性，而不是中性分子的离子特性。所有这些要点都需要仔细评估用于评估属性的方法，结果可能存在巨大差异。