Pfizer Global Supply, Pfizer Inc., Peapack, NJ 07931, USA.
Pfizer Global Supply, Pfizer Inc., Peapack, NJ 07931, USA.
Int J Pharm. 2021 Jun 1;602:120624. doi: 10.1016/j.ijpharm.2021.120624. Epub 2021 Apr 20.
One of the critical quality attributes of the solid oral dosage forms produced in continuous direct compression operations is the tablet potency. A novel soft sensor comprising of a combination of first principle-based and empirical models has been developed to enable real-time monitoring of blend and tablet potency, and concentrations of other excipients at various stream levels along the direct compression line. The soft sensor model has only three adjustable parameters, primarily associated with the equipment design and operation, so the model is product agnostic which is key to enable flexible manufacturing. The estimation accuracy of the soft sensor is demonstrated through a series of real time experiments which include steady state and dynamic transitions of potency during the runs, compared with offline analytically tested tablet cores. The results indicate that the proposed soft sensor can be utilized as a robust tool for real-time monitoring of potency, suggesting an extension of its utilization to higher levels of control. Two potential applications of the soft sensor are: 1. An element of a control strategy for product diversion; 2. A predictive model for advanced process control strategy to minimize the variability in tablet composition.
在连续直接压缩操作中生产的固体制剂的关键质量属性之一是片剂的含量。已经开发了一种新的软传感器，它由基于第一原理的模型和经验模型组合而成，能够实时监测混合和片剂含量以及直接压缩线上各个流道水平的其他赋形剂的浓度。软传感器模型只有三个可调参数，主要与设备设计和操作相关，因此该模型是产品不可知的，这是实现灵活制造的关键。通过一系列实时实验，包括运行期间的含量稳态和动态变化，与离线分析测试的片剂芯进行比较，验证了软传感器的估计准确性。结果表明，所提出的软传感器可以用作含量实时监测的强大工具，表明可以将其扩展应用于更高水平的控制。软传感器的两个潜在应用是：1. 产品转向控制策略的要素；2. 用于最小化片剂成分变异性的先进过程控制策略的预测模型。
