(344g) Real-Time Monitoring and Control of API Concentration in a Tablet Press for Continuous Manufacturing of Tablets
- Conference: AIChE Annual Meeting
- Year: 2017
- Proceeding: 2017 Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Tuesday, October 31, 2017 - 2:42pm-3:04pm
This work presents a feed-forward controller for continuous manufacturing by using a NIR-based real-time monitoring technology at a tablet press feed frame. The basic idea behind feed forward control is to measure important process variables and take corrective action before the disturbances upset the process. The feed forward controller therefore needs to receive information about the known and predictable effects of process disturbances before those occur . The proposed methodology involves measuring the inherent variability in the API concentration of material coming from the process and adjusting tablet weight to maintain overall API potency in tablets. We measured the residence time distribution (RTD) information from the rotary tablet press together with the NIR from the feed frame to develop the proposed framework as follows.
We evaluated the RTD of our Fette 1200i tablet press unit. A step change of API concentration of powder blend was given before the feed frame and the API concentration by the feed-frame NIR and compressed tablets were measured . Based on these profiles, RTD of the feed frame was shown to have a similar RTD profile as a continuous stirred tank reactor (CSTR). RTD of the turret was found to be negligibly short and no difference was observed between the profiles of the feed-frame and tablets. The estimated RTDs are useful for prediction of the CQA and its controls. The formulation for our case study consisted of micronized acetaminophen, microcrystalline cellulose (AvicelÂ® PH102), and magnesium stearate at a ratio of 15:84:1 by weight, respectively. A portable JDSU NIR probe was attached in the feed frame, sampling the powder spectra through one of the unitâs glass windows. Five (5) different blends ranging from 10 â 20% API concentration were made as calibrations for the NIR model. NIR spectra were measured in-line using the 5 powders blends to build the calibration model in situ. A calibration model with small calibration error was constructed by partial least squares (PLS) analysis. Validation experiments with four different acetaminophen concentrations demonstrated that the constructed model has high accuracy during long-term operation.
Overall, based on the feed-frameâs RTD profile and the information from the NIR sensorâs model, a feed-forward controller was developed to account for changes in powder blend API concentration and adjust tablet weight to decrease variability of API potency in tablets. It was verified by both software simulations and experiments that API potency could be maintained at the target value by the feed-forward control compared to the open-loop process.
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