(249d) A Novel Technology for Continuous Vacuum Drying of an API Slurry: Characterization of Product

Currently used drying technologies are mostly batch operations. After crystallization the API needs to be filtered and washed followed by drying. Mostly, these operations are carried out in batch, also because only very few types of equipment are available that would allow continuous operation of those processes. In recent years efforts have been made to develop and optimize continuous processes for pharmaceutical production. This development is additionally driven by the need to have fast, adaptable process equipment available. The advantage of continuous operation has been reported and discussed lately and it is important to understand that not only cost of production and advantages in scaleup drive this development.

Drying is a complex process during which various processes influence the final product properties. The properties of particles and crystals are usually well engineered during crystallization and should not be changed during the drying and filtration step. However, often agglomeration as well as attrition are observed, especially in filter bed drying. Additionally, many problems occur in this respect when considering scale up and transfer to another production site. Nonetheless this technology is often preferred because it has better drying efficiency than plate dryers because some movement is applied to the powder bed. Still this drying process can take many hours and very often yields a product that is not homogeneous and needs to be milled and sieved after production.

Part of the problem with agglomeration is the “sticky phase”. During this phase of drying the moisture content of the powder bed provides the ideal composition for agglomeration. Applied shear during this phase is crucial because too little would result in the bed hardening and too much could cause very large or hard agglomerates to be formed. Continuous technologies have the advantage that the residence time of the process is much shorter (range of minutes) combined with the fact that exposure to process conditions is more homogeneous in this intensified process.

In this work we use a different type of technology that enables continuous drying of the API slurry in industrial scale. As a test substance we used Ibuprofen, which has needle-shaped particles which are prone to attrition as well as agglomeration. To simulate the slurry, we mix the ibuprofen with a mixture of 95w%water and 5% ethanol in a ratio of 1:1 to generate a pump-able slurry. In this ratio the ethanol simulates the residual solvent in which the solubility of the substance is very high and therefore harder agglomerates could be formed. The slurry is fed with a feed rate between 1-2kg/h to the dryer via a specially developed feeding tank that enables air free undisturbed feeding of the highly viscous slurry to the dryer.

In the presentation we show the results of a DoE that was carried out to investigate the residual moisture of the API after drying in one step from slurry to below 1% residual moisture. We will show the influence on the particle size and how the “sticky phase” can be overcome without changing the initial particle size and shape.