(305b) Design of Component Particle Attributes to Optimize the Processibility of Pharmaceutical Blends

Predictive measurements of pharmaceutical powder blends intended for tabletting or encapsulation are crucial for development of robust formulations associated with few manufacturing operational issues. While assessments should ideally be conducted early in product development when the attributes of components controlling performance are still being established, processing concerns are typically manifested only at larger scales when flexibility to modify particle attributes is limited. Blend flowability is an example of an issue for which improved understanding of how component properties translate to bulk behavior in full-scale equipment is desirable.

By analysis of particle morphology, particle size, and coordination number, we present case studies revealing unexpected transitions in flowability and cohesion with changes in material properties and composition. We explore the nature of interactions between the active pharmaceutical ingredient and the excipients in the blend to explain these transitions, and optimal concentrations are identified. Hypotheses are tested by investigating the influences of geometric constraints, contact mechanics, and Van der Waals forces on glidant and lubrication effects, which in turn determine flowability performance. The resulting understanding should translate to improved design of active pharmaceutical ingredient physical properties to limit pharmaceutical manufacturability issues earlier in pharmaceutical product development.