(347a) A Continuously Recycled, Supersaturation-Controlled Crystallization Process for Precise API Psd Control for Long-Acting Injectable Suspensions

Bravecto Quantum is a long lasting injectable formulation of Bravecto (Fluralaner) providing year-long protection against fleas and ticks for dogs. It relies on a single injection of a 150mg/ml suspension of the active ingredient – Fluralaner. In the development of this formulation, an optimal API particle size was identified to improve injectability and reduce injection site reactions.

This work will present a PAT-enabled crystallization process, to produce API particles with a narrow, mono-modal size distribution, centered in a pre-specified window.

Heat-cool cycling is the typical go-to approach to increase crystal size post-crystallization. In this process, at a high level, the crystalline slurry is repeatedly heated, leading to the dissolution of smaller particles and then cooled resulting in the growth of the remaining, larger particles. As the particle size distribution, becomes narrower, however, the efficiency of heat-cool cycling diminishes.

To accelerate crystal growth and extend accessible particle sizes beyond the limit of heat-cool cycling, a process was developed relying on maintaining constant supersaturation at constant temperature by continuously recycling a portion of the slurry, heating it to dissolution and feeding it back to the crystallizer. This process allows for the reproducible, robustly controllable, and scalable manufacture of API particles in tightly controlled size windows.