TY - JOUR
T1 - Pharmaceutical hot melt extrusion process development using QbD and digital twins
AU - Matić, Josip
AU - Stanković-Brandl, Milica
AU - Bauer, Hannes
AU - Lovey, Jessica
AU - Martel, Sophie
AU - Herkenne, Christophe
AU - Paudel, Amrit
AU - Khinast, Johannes
N1 - Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/1/25
Y1 - 2023/1/25
N2 - Pharmaceutical product development guided by Quality by Design (QbD) is based on a complete understanding of the critical process parameters (CPPs) that are important for achieving the desired product critical quality attributes (CQAs). The effect of process settings, such as the screw speed, the throughput, the barrel temperature, and the screw configuration, is a well-known factor in the setup of pharmaceutical hot melt extrusion (HME) processes. A CPP that has not yet been extensively researched is the type of cross-section geometry of the screw elements. Typically, pharmaceutical extruders have double-flighted screw cross-sections, with some elements having a single- or triple-flighted element section. The exception is a NANO16 extruder from Leistritz, with all screw elements having a triple-flighted screw geometry. We investigated the process setup and scale-up to a double-flighted extruder experimentally and in silico via a digital twin. Two formulations were processed on a NANO16 extruder and virtually transferred to a ZSE18 double-flighted co-rotating twin-screw extruder. Detailed smoothed particle hydrodynamics simulations of all screw elements available from both extruders were performed, and their efficiency in conveying, pressure build-up, and power consumption were studied. Reduced-order 1D HME simulations, which were carried out to investigate the process space and scalability of both extruders, were experimentally validated.
AB - Pharmaceutical product development guided by Quality by Design (QbD) is based on a complete understanding of the critical process parameters (CPPs) that are important for achieving the desired product critical quality attributes (CQAs). The effect of process settings, such as the screw speed, the throughput, the barrel temperature, and the screw configuration, is a well-known factor in the setup of pharmaceutical hot melt extrusion (HME) processes. A CPP that has not yet been extensively researched is the type of cross-section geometry of the screw elements. Typically, pharmaceutical extruders have double-flighted screw cross-sections, with some elements having a single- or triple-flighted element section. The exception is a NANO16 extruder from Leistritz, with all screw elements having a triple-flighted screw geometry. We investigated the process setup and scale-up to a double-flighted extruder experimentally and in silico via a digital twin. Two formulations were processed on a NANO16 extruder and virtually transferred to a ZSE18 double-flighted co-rotating twin-screw extruder. Detailed smoothed particle hydrodynamics simulations of all screw elements available from both extruders were performed, and their efficiency in conveying, pressure build-up, and power consumption were studied. Reduced-order 1D HME simulations, which were carried out to investigate the process space and scalability of both extruders, were experimentally validated.
KW - 1D HME
KW - Mechanistic modeling
KW - Model validation
KW - NANO16
KW - Pharmaceutical hot melt extrusion
KW - Scale-up
KW - Smoothed particle hydrodynamics
KW - ZSE18
UR - http://www.scopus.com/inward/record.url?scp=85146041204&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2022.122469
DO - 10.1016/j.ijpharm.2022.122469
M3 - Article
C2 - 36509223
AN - SCOPUS:85146041204
SN - 0378-5173
VL - 631
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 122469
ER -