The formation of hard agglomerates during drying has impacts on the product quality, particle size distribution, and downstream formulation. Hence, understanding the cause of hard agglomerates and determining a remedy for them or preventing their formation are necessary. The integrated sorption chamber (ISC) has been successfully applied to the study of hard agglomerate formation. The design and development of this ISC are briefly described. The vapor-phase profile of a binary mixture of acetone and water without active pharmaceutical ingredient (API) was predicted using an analytical solution of a batch distillation and verified via mass spectrometry (MS). The drying of the API wet cake, which is very soluble in water, using a starting point of 5 wt % water in acetone was conducted in the ISC. A significant delay in water removal was observed from both the weight measurement and the MS signal. The slow removal of water was attributed to diffusion of water from a thin crust layer induced by the solution of the API in water and drying, resulting in the formation of hard agglomerates at the end of drying. A wet-cake solvent composition change following a cake wash with acetone reduced the initial water content from 5.5 to 0.5 wt %. This altered wet-cake solvent composition changed the behavior of water removal, leading to a significant reduction of the diffusion time. The dried API contained soft lumps without hard agglomerates.

中文翻译：

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一体化吸附室中干燥动力学的硬结块形成机理研究

干燥过程中硬质附聚物的形成会影响产品质量，粒度分布和下游配方。因此，有必要了解硬团聚的原因并确定补救措施或防止其形成。集成吸附室（ISC）已成功应用于硬质团块形成的研究。简要介绍了此ISC的设计和开发。使用分批蒸馏的分析溶液可以预测没有活性药物成分（API）的丙酮和水的二元混合物的气相分布，并通过质谱（MS）进行验证。在ISC中使用在丙酮中5 wt％的水作为起点，对非常易溶于水的API湿饼进行干燥。从重量测量和MS信号均观察到明显的除水延迟。水分的缓慢去除归因于由API在水中的溶液和干燥引起的水从薄皮层中扩散出来，并在干燥结束时形成了坚硬的团聚体。在用丙酮洗涤饼之后，改变湿饼溶剂组成将初始水含量从5.5重量％降低至0.5重量％。这种改变的湿饼溶剂组成改变了除水行为，从而导致了扩散时间的显着减少。干燥的API包含软块，没有硬团块。导致干燥结束时形成坚硬的团块。在用丙酮洗涤饼之后，改变湿饼溶剂组成将初始水含量从5.5重量％降低至0.5重量％。这种改变的湿饼溶剂组成改变了除水行为，从而导致了扩散时间的显着减少。干燥的API包含软块，没有硬团块。导致干燥结束时形成坚硬的团块。在用丙酮洗涤饼之后，改变湿饼溶剂组成将初始水含量从5.5重量％降低至0.5重量％。这种改变的湿饼溶剂组成改变了除水行为，从而导致了扩散时间的显着减少。干燥的API包含软块，没有硬团块。