Wang Zhengsong, Tang Shengnan, Yang Yanqiu, Chen Yeqiu, Yang Le
School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao 066004, China.
College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.
ACS Omega. 2023 Jun 29;8(27):24441-24453. doi: 10.1021/acsomega.3c02199. eCollection 2023 Jul 11.
In the context of Pharma 4.0, pharmaceutical quality control (PQC) is beset by issues such as uncertainties from ever-changing critical material attributes and strong coupling between variables in the multi-unit pharmaceutical tablet manufacturing process (PTMP), and how to timely adjust the operational variables to deal with such challenges has become a key problem in PQC. In this study, we propose a novel data-knowledge-driven modeling and operational adjustment framework for PTMP by integrating Bayesian network (BN) and case-based reasoning (CBR). At the modeling level, first, a distributed concept is introduced, i.e., the BN model for each subunit of PTMP is established in accordance with the operation process sequence, and the transition variables are given by the BN model established first and retrieved as the new query for the next unit. Once the BN models of all subunits are built, they are integrated into a global BN model. At the operational adjustment level, by taking the expected critical quality attributes (CQAs) and related prior information as evidence, the operational adjustment is achieved through global BN reasoning. Finally, the case study in a sprayed fluidized-bed granulation-based PTMP demonstrates the feasibility and effectiveness in improving the terminal CQAs of the proposed method, which is also compared with other methods to showcase its efficacy and merits.
在制药4.0的背景下，药品质量控制（PQC）面临诸多问题，如关键物料属性不断变化带来的不确定性以及多单元药物片剂制造过程（PTMP）中变量之间的强耦合，如何及时调整操作变量以应对此类挑战已成为PQC中的关键问题。在本研究中，我们通过整合贝叶斯网络（BN）和基于案例的推理（CBR），为PTMP提出了一种新颖的数据知识驱动的建模与操作调整框架。在建模层面，首先引入分布式概念，即根据操作流程顺序为PTMP的每个子单元建立BN模型，并由首先建立的BN模型给出过渡变量，并将其作为下一个单元的新查询进行检索。一旦所有子单元的BN模型构建完成，就将它们集成到一个全局BN模型中。在操作调整层面，以预期的关键质量属性（CQA）和相关先验信息为证据，通过全局BN推理实现操作调整。最后，在基于喷雾流化床制粒的PTMP中的案例研究证明了所提方法在改善终端CQA方面的可行性和有效性，并且还与其他方法进行了比较以展示其功效和优点。
