(656h) Effect of Intrinsic Materials Properties on the Mechanical and Rheological Behavior of API Agglomeration in Agitated Filter Dryers

The API manufacturing involves a series of processing steps including purification, filtration, drying and milling. Drying is often conducted as one of the last stages of the API production to meet the residual solvent specification, and is considered as a critical step to impact the final product performance. Among various dryer types, the agitated filter dryer (AFD) which integrates filtration and drying process into a single unit operation, is commonly used in potent API production. This single unit operation provides many advantages such as excellent containment. While agitation is required to increase heat transfer and promote homogeneity, it can cause agglomeration of wet API. The nature and material properties of the agglomerates can negatively impact the API performance during drug product processing and hence it can pose a risk to the API physical property control at the commercial scale.

Agglomeration of API during agitated filter drying is a challenging issue in pharmaceutical industry. Surface intermolecular interactions, sintering, mechanical interlocking, and formation of solid bridges have been proposed as potential mechanisms for API agglomeration. In addition, during API drying, the intrinsic API mechanical properties, surface solid-state transformation, surface features and energetics, cake wetness as well as applied external forces such as shear and compaction may lead to the formation of agglomerates and other related effects on API bulk physical properties.

In this presentation, we demonstrate an experimental approach to assess propensity of agglomeration of API particles using a mixer torque rheometer. In particular, the fundamental effect of intrinsic API particle properties on the formation of API agglomerates and resulting agglomerate properties have been investigated. By utilizing a mixer torque rheometer, we define a high risk of agglomeration (i.e. risky zone) of needle shaped API particles as a function of solvent content in a wet cake. This risky zone was demonstrated to be impacted by properties of the API as well as the solvent used. When the wet cake is agitated with a solvent content inside the risky zone, the agglomeration propensity rapidly increased, leading to increased particle size and stronger agglomerates. This work presents opportunities for better process design to avoid API agglomeration during agitated filter drying.