2013 AIChE Annual Meeting

(159f) Spherical Agglomeration of API: Screening Protocol, Process Design and Scale-Up

Authors

Dennis Ward, GlaxoSmithKline



Spherical agglomeration is a technique to grow agglomerates from already formed particles using a L-L-S system where one liquid phase preferentially wets the surface of the solid phase.

Active pharmaceutial ingredient (API) is suspended in the continuous phase, an immiscible (or partially miscible) bridging liquid is added that preferentially wets the surface of the API particles.  The process is mechanistically similar to wet granulation, including the processes of particle wetting, agglomerate growth, consolidation, and agglomerate attrition.  The process can utilize existing API particles that are resuspended or API particles can consectively be produced in-situ and agglomerated (typically with a ternary solvent system).

Spherical agglomeration can be used to produce granular API with improved bulk density and flow properties as well as improved filterability.  A generic screening protocol is presented to allow for rapid screening of spherical agglomeration conditions for water insoluble compounds.  For Compound A, process design at 100 mL scale will be discussed.  The scale up of spherical agglomeration for Compound A to 1 L and 50 L scale will then be presented and discussed.