TY - JOUR
T1 - On the influence of raw material attributes on process behaviour and product quality in a continuous wet granulation tableting line.
AU - Zupančič, Ožbej
AU - Doğan, Aygün
AU - Martins Fraga, Rúben
AU - Demiri, Valjon
AU - Paudel, Amrit
AU - Khinast, Johannes G.
AU - Spörk, Martin
AU - Sacher, Stephan
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Continuous manufacturing of oral solids is a complex process in which critical material attributes (CMAs), formulation and critical process parameters (CPPs) play a fundamental role. However, assessing their effect on the intermediate and final product’s critical quality attributes (CQAs) remains challenging. The aim of this study was to tackle this shortcoming by evaluating the influence of raw material properties and formulation composition on the processability and quality of granules and tablets on a continuous manufacturing line. Powder-to-tablet manufacturing was performed using four formulations in various process settings. Pre-blends of different drug loadings (2.5 % w/w and 25% w/w) and two BCS classes (Class I and II) were continuously processed on an integrated process line ConsiGmaTM 25, including twin screw wet granulation, fluid bed drying, milling, sieving, in-line lubrication and tableting. The liquid-to-solid ratio and the granule drying time were varied to process granules under nominal, dry and wet conditions. It was shown that the BCS class and the drug dosage influenced the processability. Intermediate quality attributes, such as the loss on drying and the particle size distribution, directly correlated with the raw material’s properties and process parameters. Process settings had a profound impact on the tablet’s hardness, disintegration time, wettability and porosity.
AB - Continuous manufacturing of oral solids is a complex process in which critical material attributes (CMAs), formulation and critical process parameters (CPPs) play a fundamental role. However, assessing their effect on the intermediate and final product’s critical quality attributes (CQAs) remains challenging. The aim of this study was to tackle this shortcoming by evaluating the influence of raw material properties and formulation composition on the processability and quality of granules and tablets on a continuous manufacturing line. Powder-to-tablet manufacturing was performed using four formulations in various process settings. Pre-blends of different drug loadings (2.5 % w/w and 25% w/w) and two BCS classes (Class I and II) were continuously processed on an integrated process line ConsiGmaTM 25, including twin screw wet granulation, fluid bed drying, milling, sieving, in-line lubrication and tableting. The liquid-to-solid ratio and the granule drying time were varied to process granules under nominal, dry and wet conditions. It was shown that the BCS class and the drug dosage influenced the processability. Intermediate quality attributes, such as the loss on drying and the particle size distribution, directly correlated with the raw material’s properties and process parameters. Process settings had a profound impact on the tablet’s hardness, disintegration time, wettability and porosity.
KW - Continuous manufacturing
KW - Fluid bed drying (FBD)
KW - Material attributes
KW - Material behaviour
KW - Powder-to-tablet
KW - Twin screw wet granulation (TSWG)
U2 - 10.1016/j.ijpharm.2023.123097
DO - 10.1016/j.ijpharm.2023.123097
M3 - Article
C2 - 37268028
AN - SCOPUS:85162155134
SN - 0378-5173
VL - 642
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 123097
ER -