Design Space Approach for the Optimization of Green Fluidized Bed Granulation Process in the Granulation of a Poorly Water-Soluble Fenofibrate Using Design of Experiment.

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 32 full-factorial design was performed to explore the effect of water amount (X1; 1-6% w/w) and spray rate (X2; 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 X1 and X2 significantly affect (p ≤ 0.05) the CQAs of granules and tablets. Particularly, X1 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 X1 and X2 at high (5.69% w/w) and low (2 g/min) levels, respectively, demonstrated the optimum operating conditions. By optimizing X1 and X2, 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.