Continuous manufacturing of pharmaceuticals offers such benefits as production flexibility, reduced drug product costs, and improved product quality. Moving toward continuous manufacturing requires suitable small-scale equipment, either by development of new equipment or optimization of existing equipment. In primary manufacturing, particle properties are often altered during crystallization and have to be restored during subsequent processing. Drying a crystallized product is one of the most challenging steps, especially since attrition and agglomeration can occur. To that end, we investigated the drying behavior of a crystalline model compound with moisture levels of up to 10 wt % in a corotating twin-screw extruder. The feed mass flows on a piece of small-scale equipment used for pharmaceutical production varied between 0.5 and 2.0 kg/h. Experiments were conducted to evaluate the drying performance in various process settings. Because of a very narrow and consistent residence time distribution, extrusion drying has the potential for pharmaceutical compound drying. In our study, we successfully accomplished drying of a crystalline product with very little agglomeration and/or attrition in some process settings while preserving a crystal size similar to that of the raw material. The reduction in particle size occurred as a result of long residence times (low extruder screw speed) and a decrease in the residual moisture of the product. The aim of our work was to show the potential of extruder drying as a novel continuous manufacturing process for pharmaceuticals and to enable further process development.

中文翻译：

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使用双螺杆挤出机连续干燥药物粉末

药品的连续生产具有生产灵活性，降低药品成本和提高产品质量等优点。走向连续制造需要适当的小型设备，或者通过开发新设备或对现有设备进行优化来实现。在初级制造中，颗粒性质经常在结晶过程中改变，并且必须在后续加工过程中恢复。干燥结晶产物是最具挑战性的步骤之一，特别是因为可能发生磨损和结块。为此，我们研究了在同向旋转双螺杆挤出机中水分含量最高为10 wt％的结晶模型化合物的干燥行为。进料质量在用于制药的一台小型设备上的流量在0.5至2.0 kg / h之间变化。进行实验以评估各种工艺设置下的干燥性能。由于非常窄且一致的停留时间分布，挤出干燥具有药物化合物干燥的潜力。在我们的研究中，我们成功地完成了晶体产品的干燥，在某些工艺条件下几乎没有团聚和/或磨损，同时保持了与原料相似的晶体尺寸。停留时间长（挤出机螺杆速度低）和产品残留水分减少的结果导致了粒径的减小。我们的工作目的是展示挤出机干燥作为药物的新型连续生产工艺的潜力，并能够进行进一步的工艺开发。