The purpose of this extensive study is to use a quality by design (QbD)
approach and multiple machine learning algorithms in facilitating wet
granulation process scale-up. This study investigated the extent of
influence of both formulation and process variables. Furthermore, measured
responses covered compressibility, compactibility and manufacturability of a
powder blend. Finally, the models developed on laboratory scale samples were
tested on pilot and commercial scale runs. Tablet detachment and ejection
work were calculated from force-displacement measurements. Significant
numerical and categorical input variables were identified by using a
stepwise regression model and their importance evaluated by using a boosted
trees model. Pilot scale runs resulted in the highest tablet tensile
strength and compaction work as well as the highest detachment and ejection
work. Critical quality attributes (CQAs) that were the most successfully
predicted were the compaction, decompaction, and net work, as well as the
tablet height. The most important input variable influencing all CQAs was
the compaction force. Application of the boosted regression trees model
resulted in the lowest Root Mean Square Error (RMSE) values for all of the
responses. This work demonstrates reliability of predictions of developed
models that can be successfully used as a part of a QbD approach for wet
granulation scale-up.
Assessment of Intragranular and Extragranular Fracture in the Development of Tablet Tensile Strength
