(539g) Continuous Fluidized Bed Drying of Pharmaceutical Materials

Recent years, the continuous manufacturing has become a trending technology in the pharmaceutical industries. Traditional batch manufacturing requires long processing times and consumes a tremendous amount of materials during process development. The US FDA is encouraging the companies to step forward into cleaner, flexible, more efficient continuous manufacturing. Although there are no regulatory hurdles for implementing continuous manufacturing, the lack of understanding of the process is limiting the integration of unit operations. Take the fluidized bed as an example; batch fluidized bed drying has been a traditional way of removing the moisture from the pharmaceutical ingredients due to its well-mixing and gentle drying behavior. The flow properties and the resulting tablet properties will be affected because of the change of moisture and particle size during the drying process. When a continuous process is adopted, the material property distribution can spread over process time. Therefore, understanding the residence time distribution is crucial to the process control.

In this study, experiments were conducted in a modified Glatt GPCG-2 continuous fluidized bed dryer/granulator. A twin-screw feeder was used to feed the wet materials. The residence time distributions for a pharmaceutical excipient (Fujicalin) and a placebo granule (Lactose/Avcil) were investigated using the colored tracer. Fujicalin is a free flowing porous material, and the Lactose/Avcil granule has very different flow properties before and after drying. The tracer concentration was calibrated and quantified with a color spectrophotometer that measures percent reflectance as a function of wavelength.[1] The residence time distribution curve was fitted by a dispersion model. The material properties were examined before and after the process. The effect of the operating conditions - material feed rate, air flow rate and initial loading were studied. The results showed that the Glatt continuous fluidized bed dryer behaved like a CSTR. The residence time could be reduced by applying a high material feed rate. The air flow rate and the initial loading did not have a significant effect on residence time for the conditions that we have investigated. As we previously found that the zero-order kinetic is dominant during the drying process, the outlet material moisture can be easily predicted by combining the RTD model and the drying kinetic.[2]

[1] Emady, H.N.; Wittman, M.; Koynov, S. et al. A simple color concentration measurement technique for powders. Powder Technology 2015,  286, 392-400.

[2] Chen, H.; Liu, X.; Bishop, C. et al. Fluidized bed drying of a pharmaceutical powder: A parametric investigation of drying of dibasic calcium phosphate. Drying Technology 2016, null-null.