Implementation of Quality by Design Case Study – Development of a process model for pulsed spray fluidised bed granulation process 


School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK


The aim of this work was to investigate the effects of different factors of pulsed frequency, binder spray rate and atomization pressure of the top-spray fluidised bed granulation process on the granule size and yield using the Box-Behnken design method. Mathematical models were developed to predict the mean size of granules and yield with high accuracy, indicating the reliability and effectiveness using the Box-Behnken experimental design method to study the fluidised bed granulation process.


Quality by design (QbD) has been introduced in the pharmaceutical industry with the aim of building quality into the product right from the formulation development to the manufacturing processes, which has been defined in the ICH Q8 guideline as “a systematic approach to development that begins with predefined objective and emphasizes product and process understanding and process control, based on sound science and quality risk management” (1). The key elements of QbD include: a) define target product quality profile; b) design and develop product and manufacturing processes; c) identify critical quality attributes, process parameters, and sources of variability and d) control manufacturing process to produce consistent quality over time. Understanding of the product and manufacturing process is essential in the concept of QbD, which includes understanding the impact of raw material attributes and process parameters on the critical quality attributes and identification and control of sources of variability. Therefore design space of the process parameters within which the critical quality attributes of the product remain within specifica ...