(406c) Development of Controlled Agglomeration During Vacuum Agitated Filter Drying for An Active Pharmaceutical Ingredient

In the pharmaceutical industry, agitated filter dryers are used for the isolation and drying of active pharmaceutical ingredients (APIs).  A typical drying process has two stages: blowdown, during which filtered nitrogen is passed through the wet API cake to achieve a target solvent level, and agitated vacuum drying, during which vacuum is used to pull off solvent while the wet cake is agitated.  This agitated drying can impact the effective particle size through attrition, where a reduction in the primary particle size is observed, and agglomeration, where groups of primary particles bind together to form larger ones.  Uncontrolled agglomeration, commonly referred to as balling, occurs when agitated drying begins with too high a solvent concentration in the wet cake.  Balling is the formation of very large, dense agglomerates with widely varying sizes, the largest of which can damage drying equipment if undetected.  Acicular APIs (high-aspect ratio, needle-like particles) often encounter uncontrolled agglomeration during drying.  Developing a better understanding of the agglomeration process can lead to improved control to avoid balling and yield agglomerates with improved flow properties as compared to unagglomerated acicular APIs.  

In this study, an innovative drying process was developed to increase the bulk density and flow properties of acicular needles via a controlled agglomeration process. Initial scoping studies were performed using  powder rheometry to identify appropriate solvent levels for the initiation and control of agglomeration.  Drying experiments were carried out at 1 L, 2 L, and 50 L scale using API that was recrystallized and wet-milled with a rotor-stator mill.  The wet-milled API batches were agitated at various “go-drying” loss-on-drying levels identified from the powder rheometry experiments.  The knowledge gained from this study was successfully used to control agglomeration of primary particles upon scale up to pilot plant scale.