(315d) Formulation and Scale-up of Fast-Dissolving Lumefantrine Nanoparticles for Oral Malaria Therapy
AIChE Annual Meeting
2022
2022 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Drug Delivery
Tuesday, November 15, 2022 - 1:24pm to 1:42pm
We report the development of a LMN nanoparticle formulation and the translation of that formulation from laboratory to industrial scale. We applied Flash NanoPrecipitation (FNP) to develop nanoparticles with 90% LMN loading with sizes of 200-250 nm. The final powders are readily redispersible and are stable over accelerated aging conditions (50°C, 75% RH, open vial) for 4 weeks giving equivalent and fast drug release kinetics in both simulated fed and fasted state intestinal fluids making them suitable for pediatric administration. The nanoparticle-based formulations increase the bioavailability of lumefantrine 4X in vivo when compared to the control crystalline formulation. The three continuous processes (FNP, tangential flow ultrafiltration, and spray drying) were optimized at small and pilot scale to produce the nanoparticles. We describe the translation of the laboratory-scale process at Princeton University to the clinical manufacturing scale at WuXi AppTech (Shanghai, China).