(457e) Trouble-Shooting of Glassy and Ball Material Formulation during Drying of Api Wet Cake

The API wet cake, isolated from a mixture of water, ethanol, and small percentage of other solvents, has a LOD around 50% and is dried with an agitated drier under vacuum and heat. The dried API from the agitated drier in production typically produces some glassy and ?ball? shaped materials as large as golf balls, which makes the drying operation less efficient and subsequent milling operation difficult.

The purpose of this investigation was to determine the root-causes of the glassy and ball material formation and to develop a proper procedure to minimize or eliminate them in production. Many drying experiments using a lab scale agitated dryer were conducted to mimic the production drier, and drying simulation was also performed. It was concluded that the glassy and ball formation during drying is mainly caused by the condensation of ethanol and water vapor that locally and partially dissolves the API and initiates the balling. This is especially true at the beginning of the drying cycle where vapor is enriched with ethanol (wet cake typically contains about 10% ethanol and 40% water and API is very soluble in ethanol). The condensation could take place in the drier headspace and along the path of vacuum line where temperatures are below the internal temperature of the drier.

Local vapor condensation also takes place at the beginning of drying when there is a large temperature difference between the jacket wall and the bulk. At the plant the jacket temperature is increased from room temperature to 70°C quickly, and there is a large temperature gradient between the wall and the bulk of the drier. Part of the vapor evaporated near the wall or heated shaft was diverted to the cooler location and condensed there. This condensate, enriched in ethanol, dissolve the API and form sticky glassy materials that initiate the ball formation. In this presentation, we will discuss in details the procedure and results to eliminate this glassy and ball materials in commercial production.

After implementing the process optimization, the glassy and large balls were totally eliminated in production, the drying cycle time was also significantly reduced by over 25%. This significantly increases the throughput of the this bottleneck step in commercial production.