TY - JOUR
T1 - Process Optimization and Upscaling of Spray-Dried Drug-Amino acid Co-Amorphous Formulations
AU - Kasten, Georgia
AU - Duarte, Íris
AU - Paisana, Maria
AU - Löbmann, Korbinian
AU - Rades, Thomas
AU - Grohganz, Holger
PY - 2019/1/1
Y1 - 2019/1/1
N2 - The feasibility of upscaling the formulation of co-amorphous indomethacin-lysine from lab-scale to pilot-scale spray drying was investigated. A 2 2 full factorial design of experiments (DoE) was employed at lab scale. The atomization gas flow rate (F atom , from 0.5 to 1.4 kg/h) and outlet temperature (T out , from 55 to 75 ◦ C) were chosen as the critical process parameters. The obtained amorphization, glass transition temperature, bulk density, yield, and particle size distribution were chosen as the critical quality attributes. In general, the model showed low F atom and high T out to be beneficial for the desired product characteristics (a co-amorphous formulation with a low bulk density, high yield, and small particle size). In addition, only a low F atom and high T out led to the desired complete co-amorphization, while a minor residual crystallinity was observed with the other combinations of F atom and T out . Finally, upscaling to a pilot scale spray dryer was carried out based on the DoE results; however, the drying gas flow rate and the feed flow rate were adjusted to account for the different drying chamber geometries. An increased likelihood to achieve complete amorphization, because of the extended drying chamber, and hence an increased residence time of the droplets in the drying gas, was found in the pilot scale, confirming the feasibility of upscaling spray drying as a production technique for co-amorphous systems.
AB - The feasibility of upscaling the formulation of co-amorphous indomethacin-lysine from lab-scale to pilot-scale spray drying was investigated. A 2 2 full factorial design of experiments (DoE) was employed at lab scale. The atomization gas flow rate (F atom , from 0.5 to 1.4 kg/h) and outlet temperature (T out , from 55 to 75 ◦ C) were chosen as the critical process parameters. The obtained amorphization, glass transition temperature, bulk density, yield, and particle size distribution were chosen as the critical quality attributes. In general, the model showed low F atom and high T out to be beneficial for the desired product characteristics (a co-amorphous formulation with a low bulk density, high yield, and small particle size). In addition, only a low F atom and high T out led to the desired complete co-amorphization, while a minor residual crystallinity was observed with the other combinations of F atom and T out . Finally, upscaling to a pilot scale spray dryer was carried out based on the DoE results; however, the drying gas flow rate and the feed flow rate were adjusted to account for the different drying chamber geometries. An increased likelihood to achieve complete amorphization, because of the extended drying chamber, and hence an increased residence time of the droplets in the drying gas, was found in the pilot scale, confirming the feasibility of upscaling spray drying as a production technique for co-amorphous systems.
U2 - 10.3390/pharmaceutics11010024
DO - 10.3390/pharmaceutics11010024
M3 - Journal article
C2 - 30634423
SN - 1999-4923
VL - 11
JO - Pharmaceutics
JF - Pharmaceutics
IS - 1
ER -