Chapter 30 - Process Development, Optimization, and Scale-up: Fluid-bed Granulation

Abstract

Fluid-bed granulation is a widely used and well-characterized unit operation in the pharmaceutical industry. A fluid-bed wet granulation process consists of dry blending, wet granulation, and drying steps. Moisture profiling throughout the process can be used as a fingerprint for the formulation and process and it is also useful for process development and trouble shooting purposes. When wet granules contact the hot inlet air, the hot inlet air exchanges its heat for moisture. In the drying process, moisture in wet granules is removed by dry inlet air. During wet granulation, there is another source of moisture, which is sprayed binder solution. To predict moisture balance during the wet granulation process, there are two parameters that need to be taken into consideration—moisture removed, and moisture accumulated in the wet granules for the wet granulation process. Many variables can impact manufacturability and product quality in the fluidized-bed wet granulation process. In order to develop a robust process, it is necessary to evaluate the effects of these variables at an early stage. These variables can be classified into three groups—equipment related, formulation related, and process related variables.