(746a) Application of Radiometric Sensor for Inline Mass Flow Rate Monitoring and Control of a Continuous Tablet Manufacturing Line

Ganesh, S., Purdue University
Reklaitis, G. V., Purdue University
Nagy, Z. K., Purdue University
Su, Q., Purdue University
The accelerating research in continuous pharmaceutical manufacturing has already resulted in approval for two drug products produced via continuous manufacturing in 2016 by the US-FDA [1]. The two approvals and more filings for continuous manufacturing of drug product reflects the growing interest by pharmaceutical manufacturers and the regulatory body in the shift of manufacturing towards continuous operations. The implementation of an integrated tablet manufacturing process in continuous operation requires effective real time process management [2]. This involves integration of real time process data of the operation parameters and the quality attributes of intermediate blends, granules and tablets, from online and soft sensors into a model based and data driven framework.

The first step in the tableting process is to ensure blend uniformity and desired throughput from the continuous feeding and blending of excipients and API. Quality specifications at the outlet of the blender can be achieved by implementing ratio control of the feed streams [3]. This requires continuous monitoring of blend composition and mass flow rate at the outlet for implementation of the ratio control framework. Additionally, it is desirable to monitor the mass flow rate at the inlet of the tablet press, as the system could have material losses or bulk density variations by virtue of multiple processing units. This would enable implementation of robust feed forward and advanced control structures for the tableting operation. This work focusses on critical evaluation of a radiometric sensor for mass flow rate monitoring of particulate flow in continuous manufacturing of tablets using dry powder feeds.

The radiometric sensor, developed by Enurga Inc., (West Lafayette, IN) is based on x-ray attenuation and cross correlation velocimetry [4]. The monitoring technique is non-invasive and implemented for on-line monitoring of mass flow rate [5]. The sensor is evaluated for its capability to monitor mass flow rate in real time for the materials and operating conditions similar to that handled in the pilot plant facility at Purdue University. The mass flow rate is observed to be linearly proportional to the attenuation of x-rays by the material flowing through the sensor.

The performance of the sensor primarily depends on material handling and flow properties. The measurement precision for powder blends comprising of varying proportions of acetaminophen (APAP), microcrystalline cellulose (MCC) and lactose is evaluated. The sensor gives a precise measurement of the attenuation of the x-rays, with the same proportionality constant for 0 to 10% of APAP and MCC mixtures and 6 to 11 kg/h. The variance of measurement is higher at lower flow rates and for materials with poor flow. The sensor accuracy in real time is evaluated by monitoring flow rate with sampling at every second using MCC and a granulated sample of acetaminophen and MCC. The x-ray attenuation for a given material is calibrated over a known flow rate range. The sensor is used for monitoring a different flow rate in the range and compared with the measured flow using direct weighing. The flow rate monitored by the sensor depends on the calibration, measurement variance and material flow properties. The measured flow rate is observed to be within 5% of the actual flow rate [6].

After substantial offline testing, the sensor has been integrated into the tableting line and demonstration of real time monitoring and control of the feeder-blender unit will be reported. The added sensor provides needed redundancy in measurement of process variables in order to enable data reconciliation for the process line.


  1. https://blogs.fda.gov/fdavoice/index.php/2016/04/continuous-manufacturin...
  2. Giridhar A, Gupta A, Louvier M, Joglekar G, Nagy ZK, Reklaitis G V. Intelligent Process Management for Continuous Operations in Pharmaceutical Manufacturing. 24th Eur Symp Comput Aided Process Eng. 2014;33:391-396.
  3. Moreno M, Reklaitis G V., Nagy ZK. Systematic Framework for the Design and Analysis of Control Systems for Continuous Pharmaceutical Manufacturing. In: AIChE Annual Meeting. Salt Lake City; 2015
  4. Personal communication with Jongmook Lim, Enurga Inc., West Lafayette, IN
  5. Barratt, I. R., Yan, Y., Byrne, B., & Bradley, M. S. A. (2000). Mass flow measurement of pneumatically conveyed solids using radiometric sensors, 11, 223–235.
  6. Ganesh S., Troscinski R., Schmall N., Nagy Z., Reklaitis G., In-line and non-invasive monitoring of mass flow rate using x-ray sensor in continuous tableting line, In Preparation