(366a) Continuous Mixing Technology: The Impact of Blend Properties and Process Parameters on Mixing Performance

Continuous powder mixing technology application during continuous direct compression process has emerged as a leading technology used in the development and manufacture of solid oral dosage forms [1, 2]. The critical quality attributes (CQAs) of the final product is heavily depending on the performance of the mixing step as the quality of mixing will directly influences the content uniformity of the tablet.

Therefore, the aim of this study was to investigate the impact of blend properties (bulk density, API sizes) and process parameters (process throughput, hold up mass and impeller speed) on the mixing performance. Mixing performance was characterized using the residence time distribution (RTD) of the process, which has been broadly used to characterize unit operations in pharmaceutical processes. In this work, the RTDs for a vertical continuous mixing device termed Continuous Mixing Technology (CMT) were obtained in order to evaluate mixing performance over a defined operating space. The RTDs were determined using a spike injection of tracer material into the mixer and measuring the concentration of the tracer in the outgoing material. This was achieved using a PAT interface situated at the exit of the CMT that presents the material to a near-infrared (NIR) probe. The theoretical residence time of the mixer is given by the hold-up mass divided by the throughput [1], and for each experiment, NIR spectra of the exiting material was measured for five theoretical residence times after tracer injection to obtain the full RTD.

As the CMT contains an upper de-lumping screen and a lower mixing chamber, the residence time distributions of this system can be described as two CSTRs in series with different residence times [1] where the parameter ‘r’ describes the ratio between these residence times. The best value of ‘r’ for all experiments was determined through simultaneous optimization of all measured RTDs. The results showed that the CMT operates close to a single CSTR over the whole operating space, has good ability to dampen the fluctuations from the gravimetric feeders, and that the mixing performance of the CMT is not significantly impacted by blend properties (i.e. bulk density and API particle size).

References:

[1] Blackwood, D.O., Bonnassieux, A. and Cogoni, G. Continuous Direct Compression Using Portable Continuous Miniature Modular & Manufacturing (PCM&M). In Chemical Engineering in the Pharmaceutical Industry: Drug Product Design, Development, and Modeling, 2nd Edition, am Ende, T., am Ende, D. J., Wiley, 2019, pp 547-560.

[2] Markarian, J. (2 April 2018). Modernizing Pharma Manufacturing. www.pharmtech.com