Soft sensor for real-time estimation of tablet potency in continuous direct compression manufacturing operation.

[Display omitted] • A novel hybrid soft sensor for monitoring blend potency along continuous direct compression line. • Capable of estimating tablet potency with R2 = 96% linearity across 85%-115% potency range. • Application in control strategy for product diversion and APC to minimize variability in potency. 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. [ABSTRACT FROM AUTHOR]