Application of definitive screening design to quantify the effects of process parameters on key granule characteristics and optimize operating parameters in pulsed-spray fluid-bed granulation

The pulsed-spray fluid-bed granulation (PSFBG) process was investigated and optimized using definitive screening design, a recently proposed new class of three-level design of experiment method. Such a design enabled quadratic models to be established that described the effect of six input process parameters – inlet air temperature, inlet air humidity, binder spray rate, atomization pressure, pulse period, and pulse width – on the granule quality in a PSFBG process. Mathematical models of the mean particle size, relative size distribution width, production yield, and porosity were developed to quantify the relationships between the influencing factors and critical quality attributes. On the basis of constraints on the desired granule properties, a design space for PSFBG was determined and ranges of the operating parameters were defined. An acceptable degree of prediction was confirmed by validation experiments, demonstrating the reliability and effectiveness of using definitive screening design to study the PSFBG process. This method can accelerate screening and optimization of this process within a large multidimensional design space.