Single-crystal Drying: Development of a Continuous Drying Prototype to Optimize Particle Flow and Residence Time Distribution

Purpose: In the pharmaceutical industry, there has been a growing interest in continuous manufacturing in recent years. Many efforts have been made to implement new process equipment for various production steps. One step which is not yet covered well is the continuous drying of the active pharmaceutical ingredient (API) after it has been crystallized with the desired particle properties. The dryer prototype, developed in this study, can operate continuously with poorly flowable materials. Methods: After initial testing of a paddle dryer, an optimized prototype was designed and built. Ibuprofen and di-calcium phosphate were used as test substances. Ibuprofen was used because of its bad processability due to poor flowability and very low melting point. This makes it well-suited for simulating other APIs as a worst case. Di-calcium phosphate has a very good flow behavior and represents the other extreme of the plausible flow properties. Results: In the paddle dryer, significant accumulation led to an unstable residence time distribution (RTD). Hence, the dryer was unsuitable for non-ideal pharmaceutical products. However, the product properties were very promising (i.e., little to no attrition and almost no agglomeration, as well as dry product); therefore, a new dryer design was developed. As a result, the undesired accumulation of material in the dryer was significantly reduced. The introduction of a gentle, forced flow improved the RTD, and it was possible to run the dryer continuously for extended periods of time (5.5 h), with a stable holdup. Conclusion: The optimized flow of powder within the newly developed dryer does not only enable continuous drying but also reduces the drying time (in comparison with batch) and guarantees that the individual particle is dried without change. Further work with different materials and process conditions should follow, to evaluate the applicability of the dryer as sustainable technology.