Multiple approaches to reduce reconstitution time of lyophilized drug products with high protein concentration.

BACKGROUND: Lyophilized drug products with high protein concentration often perform long reconstitution time, which is inconvenient for clinical use. The objective of this work is to achieve short reconstitution time with multiple and combined strategies. METHODS: Here, we describe the following approaches that lead to reduction of reconstitution time, including adding annealing step, decreasing headspace pressure, decreasing protein concentration with reducing diluent volume, increasing high surface-area-to-height ratio of the cakes, increasing frequency of swirling and diluent temperature. RESULTS: Among these strategies, reducing diluent volume to achieve high protein concentration and reducing headspace pressure show markedly reduction of reconstitution time. Moreover, we propose combined strategies to mitigate the reconstitution time, at the same time, to achieve same target dose in clinics. CONCLUSIONS: Therefore, this paper provides insights on the application of multiple strategies to accelerate the reconstitution of lyophilized drug products with high concentration, and facilitates their widespread clinical application.