Industrial-Scale Continuous Vacuum Drying of Active Pharmaceutical Ingredient Paste: Determination of the Process Window

Abstract

Many efforts have been made in recent years to adopt and implement continuous processing into the pharmaceutical production chain, driven by the desire to optimize the process efficacy and cost as well as the product quality. In the current challenging times, the need for fast adaptable processes to enlarge and facilitate the drug production on short notice is even more immanent than before. Suitable equipment for some unit operations is still missing. Drying is one of those and one of the most complex processes in the active pharmaceutical ingredient (API) manufacturing chain. Drying can influence the surface structure, particle size, as well as the morphology, in the worst case even causing degradation, especially in heat-sensitive substances. When producing APIs by proper design of the crystallization process to the desired target properties, it is key to have a drying process that can remove residual liquids without changing the particles. Practically, this means not changing particle size distribution by neither agglomeration nor particle attrition. In this work, the process window of a process, enabling full-scale continuous drying of a crystalline API after crystallization and washing, was investigated. An Ibuprofen paste containing water and ethanol as a liquid phase has been dried in a continuous vacuum dryer. The particles undergo no change during the process, and the needle-shaped particle form as well as the volume mean diameter of ∼80 μm was maintained until the end of the process for a large process window. Furthermore, it was shown that this continuous process can be run successfully in a semicontinuous mode, which enables implementing this new process into the existing batch operating manufacturing plants. The process time is much faster as for conventional batch drying technology, and the product volume can be scaled via run time or the throughput, therefore enabling a fast response to change in drug demand.