(509g) Investigation of Electric Capacitance-Based and X-Ray-Based Sensors for Real-Time Mass Flow Rate Monitoring in Continuous Tablet Manufacturing

Huang, Y. S., Purdue University
Reklaitis, G. V., Purdue University
Nagy, Z. K., Purdue University
Ganesh, S., Purdue University
Marashdeh, Q., Tech4Imaging Inc
Zuccarelli, C., Tech4imaging
The adoption of continuous pharmaceutical manufacturing is accelerating with six solid oral drug products produced via continuous tablet manufacturing approved by the FDA to date[1-3]. To continue the shift from batch operations to continuous operations to a wider range of products, using more complex routes such as wet and dry granulation, further advances in real-time process management (RTPM) are necessary. The key challenge in RTPM is to capture real-time data of critical process parameters (CPP) and critical quality attributes (CQA) of materials in a robust and accurate fashion so as to inform real-time manufacturing decisions.

The mass flow rate of particulate materials is an important CPP which affects the concentration and the content uniformity of the final product. Those attributes depend on the relative amounts of active pharmaceutical ingredients (API) and excipients which are combined into the powder blend. While loss-in-weight feeders can generally deliver granular materials at specified set points, mitigation of flow disturbances requires the implementation of the ratio control strategies [4] which depend on actual flow measurements. Moreover, mass flow measurements are important to establish whether the process is in a state of control and whether material losses or material accumulations are taking place in the process. This work is focused on investigating the use and comparative performance of Electrical Capacitance Volume Tomography (ECVT) sensor as well as an X-ray based sensor for real-time measurement of mass flow of powder/granular flows.

Our study draws on previous work reported in Ganesh et al [5] on the X-ray based sensor. The sensor, manufactured by Enurga Inc., (West Lafayette, IN) is based on X-ray attenuation and cross-correlation velocimetry [6]. When used in measuring powder blends composed of different proportions of acetaminophen (APAP), microcrystalline cellulose (MCC), lactose, magnesium stearate and silicon dioxide, the research indicated that the measured mass flow rate was within 5% of the actual mass flow rate in the pilot plant at Purdue University [5]. Although the measurement provided acceptable accuracy, the restriction where the X-ray sensor can be located by virtue of the requirement of bulky shielding has motivated the investigation of alternative technologies.

The ECVT sensor, offered by Tech4Imaging LLC, (Columbus, OH) is based on reconstruction of capacitance data [7]. It is a non-invasive sensing technology with fast data acquisition which makes it a good potential candidate for monitoring a continuous tablet manufacturing line. The ECVT sensors measure the dielectric properties of the particulate flow. A novel mapping between the change in capacitance and the displacement of materials affected by sensor sensitivity gradient is used to determine the displacement profile, and hence the velocity profile, which no longer depends on cross-correlation velocimetry [7]. Combined with volume fraction obtained from reconstruction of capacitance data, the velocity profile of solids is further transformed into real-time mass flow rate measurement.

In the first part of this study, we report on the performance of the sensor in a stand-alone system consisting of a loss-in-weight feeder, the ECVT senor and an independent gravimetric measurement. In the second part of this study, the ECVT sensor will be integrated into the tableting line at two locations – the exit of the API-excipient feeder-blender system and the entry to the tablet press. The performance of the ECVT sensor will be compared to that of the X-ray sensor for delivering the same functionality and the relative advantages and limitations of these technologies summarized.


  1. Ned Pagliarulo. (2018) Pharma's slow embrace of continuous manufacturing. Available at: https://www.biopharmadive.com/news/pharmas-slow-embrace-of-continuous-manufacturing/532811
  2. Pfizer Inc. (2018).S. FDA Approves DAURISMOâ„¢ (glasdegib) for Adult Patients with Newly-Diagnosed Acute Myeloid Leukemia (AML) for Whom Intensive Chemotherapy is Not an Option. Available at: https://www.marketwatch.com/press-release/us-fda-approves-daurismotm-glasdegib-for-adult-patients-with-newly-diagnosed-acute-myeloid-leukemia-aml-for-whom-intensive-chemotherapy-is-not-an-option-2018-11-21
  3. Lawrence De Belder, (2019) IFPAC Presentation. Information of Drug product is available at: https://www.janssen.com/canada/sites/www_janssen_com_canada/files/prod_files/live/tramacet_cpm.pdf
  4. Lakerveld, R., Benyahia, B., Braatz, R. D., & Barton, P. I. (2013). Model-based design of a plant-wide control strategy for a continuous pharmaceutical plant. AIChE Journal, 59(10), 3671-3685.
  5. Ganesh, S., Troscinski, R., Schmall, N., Lim, J., Nagy, Z., & Reklaitis, G. (2017). Application of X-ray sensors for in-line and noninvasive monitoring of mass flow rate in continuous tablet manufacturing. Journal of pharmaceutical sciences, 106(12), 3591-3603.
  6. Yan, Y. (1996). Mass flow measurement of bulk solids in pneumatic pipelines. Measurement Science and Technology, 7(12), 1687.
  7. Chowdhury, S., Marashdeh, Q. M., & Teixeira, F. L. (2016). Velocity profiling of multiphase flows using capacitive sensor sensitivity gradient. IEEE Sensors Journal, 16(23), 8365-8373.