集成群体平衡与多物理场建模用于预测小分子制造中不期望的团聚

中文摘要 AI 辅助

搅拌过滤干燥器（AFDs）是小分子制造中的关键单元操作，能够同时实现活性药物成分的过滤、洗涤和干燥。AFDs面临的关键挑战之一与不期望的团聚相关，其中硬团聚体的存在导致不合格产品、设备损坏以及额外的下游处理。本文提出了一种新颖的机理模型，描述了搅拌过滤干燥过程中软团聚体和硬团聚体的形成。通过集成群体平衡和多物理场建模，该模型能够准确预测产品温度、水分含量和粒径分布的演变，从而量化不同操作条件下不期望团聚的程度和影响。我们提出的基于模型的框架能够实现AFDs的合理设计和操作，以提高产品质量和工艺可靠性。

英文摘要

Agitated filter dryers (AFDs) are a crucial unit operation in small molecule manufacturing that enables simultaneous filtration, washing, and drying of active pharmaceutical ingredients. One of the key challenges in AFDs is associated with undesired agglomeration, where the presence of hard agglomerates results in off-spec products, equipment damage, and additional downstream processing. This article presents a novel mechanistic model that describes the formation of soft and hard agglomerates during agitated filter drying. By integrating population balance and multiphysics modeling, the model can accurately predict the evolution of the product temperature, moisture content, and particle size distribution, and hence quantify the extend and impact of undesired agglomeration across various operating conditions. Our proposed model-based framework enables the rational design and operation of AFDs for improving the product quality and process reliability.

发表机构

• Massachusetts Institute of Technology（麻省理工学院）
• Takeda Development Center Americas, Inc.（武田美洲开发中心有限公司）

机构由 AI 辅助整理，请以论文原文为准。