Abstract
In the pharmaceutical industry, the systematic optimization of process variables using a quality-by-design (QbD) approach is highly precise, economic and ensures product quality. The current research presents the implementation of a design-of-experiment (DoE) driven QbD approach for the optimization of key process variables of the green fluidized bed granulation (GFBG) process. A 3
2
full-factorial design was performed to explore the effect of water amount (X
1
; 1–6%
w
/
w
) and spray rate (X
2
; 2–8 g/min) as key process variables on critical quality attributes (CQAs) of granules and tablets. Regression analysis have demonstrated that changing the levels of X
1
and X
2
significantly affect (
p
≤ 0.05) the CQAs of granules and tablets. Particularly, X
1
was found to have the pronounced effect on the CQAs. The GFBG process was optimized, and a design space (DS) was built using numerical optimization. It was found that X
1
and X
2
at high (5.69%
w
/
w
) and low (2 g/min) levels, respectively, demonstrated the optimum operating conditions. By optimizing X
1
and X
2
, GFBG could enhance the disintegration and dissolution of tablets containing a poorly water-soluble drug. The prediction error values of dependent responses were less than 5% that confirm validity, robustness and accuracy of the generated DS in optimization of GFBG.