(129a) Investigation of Different Continuous Drying Routes for Pharmaceuticals

Batch processing was the state of the art production route for pharmaceuticals during the last decades. Although widely established, this way of manufacturing has some drawbacks such as higher footprint of the entire production site, complex logistics, limited possibilities for in-line process control and cost intensive scale-up. In order to increase robustness, flexibility and cost-effectiveness of manufacturing, academia, industry and regulators have been pushing the development of fully continuous lines. Continuous processing allows utilization of the same equipment for process development as well as for the final production process. In addition, robust product quality can be guaranteed by an in-process quality control. A full continuous pharmaceutical manufacturing facility may include API synthesis as well as manufacturing of the final dosage form. A broad range of continuous manufacturing equipment is already on the market for various unit operations, but there is still a gap to link primary and secondary manufacturing.

One of those challenging process steps between primary and secondary manufacturing is the continuous drying of API’s. During API synthesis and subsequent crystallization the desired particle properties, such as size and morphology, are tailored. However, during washing and drying these properties can be changed, due to attrition and agglomeration. Therefore, the challenge during drying is to minimize such effects.

This presentation will highlight results of drying experiments with two different drying technologies. APIs and excipients with a particle size below 100 µm were dried either based on extrusion or contact-convective drying technology. Variation in process settings was tested and successful configurations were found. Feed materials with different initial moisture content were processed to evaluate the drying capacity of the two dryer options. Measurements of particle size distribution, residual moisture content and flowability were conducted. Residual moisture of the dried products reached levels below 0.1%. No change in particle size distribution for the tested APIs was observed and therefore no agglomeration or attrition occurred during the drying procedure. In addition, powder flowability showed similar results prior and after drying.

The key to successful continuous drying of powders and matching specified product quality is a robust process design with consistent processability. This includes avoiding of dead zones, resulting in a narrow residence time distribution (RTD), amongst others. A narrow RTD leads to less mixing of particles with different moisture levels and results in a reduced tendency of agglomeration or attrition.