Improving the Manufacturability of Cohesive and Poorly Compactable API for Direct Compression of Mini-tablets at High Drug Loading via Particle Engineering.

Abstract

To utilize a particle engineering strategy to improve the manufacturability of a cohesive and poorly compactable API at high drug loading for direct compression of mini-tablets. A high-shear mixer was used for wet milling during the API manufacturing process to obtain target particle size distributions. The targeted particles were characterized and formulated into blends by mixing with excipients. The formulated blends were compressed directly into mini-tablets using a compaction simulator. The tablet hardness, weight variation, and friability of the mini-tablets were characterized and compared with mini-tablets prepared with hammer milled APIs. Compared to the hammer milled APIs, the wet milled APIs, had smoother surface, narrower particle size distributions and demonstrated a better flow properties. Moreover, the mini-tablets produced with the wet milled APIs exhibited better weight uniformity, robust tablet mechanical strength and ultimately better friability. In addition, unlike the hammer milled process, the wet milling process is controllable and easy to scale up. This study successfully implemented API particle engineering through a high shear wet milling process to produce particles suitable for robust drug product manufacturing.