(273a) The Interplay of Component Size, Morphology and Gelatinization On the Flow Performance of An Encapsulated Pharmaceutical Blend

Nakagawa, H., Merck & Co., Inc
Conway, S. L., Merck & Co., Inc.
Goldfarb, D., Research done at Exxon Corporate Research

Understanding the flow properties of a pharmaceutical powder blend intended for formulation in a gelatin capsule is crucial for proper process design and robustness, and avoidance of weight uniformity issues that can ultimately impact safety and efficacy. We conduct physical characterization of severl component lots and blend compositions to determine that the flowability for a series of prototype formulations is highly variable. In attempting to understand the underlying causes of the variability, we discover unexpected transtions in flow properties as a result of changing drug load. The interactions between the active pharmaceutical ingredient and the excipients in the blend are shown to cause these transtions, and optimal concentrations are identified. The potential roles individual components as glidants is shown to depend on factors such as gelatization extent, particle morphology and particle size distribution. General blend design strategies for improved flow performance are explored.