Application of X-Ray Sensors for In-line and Noninvasive Monitoring of Mass Flow Rate in Continuous Tablet Manufacturing

作者：Ganesh Sudarshan^*; Troscinski Rachel; Schmall Nicholas; Lim Jongmook; Nagy Zoltan; Reklaitis Gintaras

来源：Journal of Pharmaceutical Sciences, 2017, 106(12): 3591-3603.

DOI：10.1016/j.xphs.2017.08.019

• Solid dosage form
• Tableting
• Processing
• Powder technology
• PAT tools
• Quality by design
• Real-time process monitoring

The progress in continuous downstream manufacturing of oral solid doses demands effective real-time process management, with monitoring at its core. This study evaluates the feasibility of using a commercial sensor to measure the mass flow rate of the particulates, a critical process variable in continuous manufacturing. The sensor independently measures X-ray attenuation and cross-correlation velocimetry of particulate flow in real time. Steady-state flow rates of blends comprised primarily of acetaminophen and microcrystalline-cellulose are monitored using the sensor, with simultaneous weighing scale measurements, to calibrate the sensor and investigate the measurement accuracy. The free-fall flow measurement of the powder and granule blends in a conduit is linearly proportional to the X-ray attenuation. Relative standard deviations of similar to 3%-7% for 1 s monitoring are observed and a measurement error of approximately 5% suggests the usability of the sensor for real-time monitoring. The sensor measurement is robust for operational variations in composition, addition of lubricant or glidant and reuse of material for PAT tool calibration. The measurement relative standard deviations depend on particulate flow dynamics at the sensor location. This requires experimental evaluation for a given material at the sensor location, to capture the flow dynamics of the particulate stream through the sensor.

• 出版日期2017-12