**3. FbD methodology**

The theme of FbD optimization methodology provides thorough and thoughtthrough information on diverse aspects, organized in a five-step sequence, as schematically depicted in **Figure 2**.



## *Formulation by Design: An Overview DOI: http://dx.doi.org/10.5772/intechopen.109702*


#### **Table 2.**

*Important terms used in the formulation by design of pharmaceutical drug delivery:*

**Figure 1.** *Inter-relationship among knowledge, design and control spaces.*

**Figure 2.**

*Schematic representation of FbD optimization methodology.*

may be accomplished by carrying out the risk assessment and quality risk management (QRM) approach by earmarking the severity of risk, its frequency of occurrence and detectability associated with each input variable. For that, the moderate to high risk factors are chosen from patient perspectives through brainstorming among the team members using techniques like risk estimation matrix (REM), failure mode effects analysis (FMEA). These techniques help in identifying and sorting the potential risk associated with each CMA as applicable to the identified CQAs. Selection of "vital few" influential factors among the "possible many" input variables is invariably conducted using experimental designs through a process, popularly termed as factor screening. In a nutshell, screening exercise tends to help the scientist in opting the "leader" variables, while weeding out the "idler" ones. By and large, low-resolution firstorder designs (like full-factorial and fractional factorial, Plackett-Burman, Taguchi designs) suffice the purpose of screening of a large number of experimental parameters. Experimental studies are also undertaken to define the broad range of factor levels. Apt use of screening designs, in this regard, helps to identifying the potential CMAs actually affecting the CQAs and reducing their number.


The optimum formulation is scaled up through a pilot plant, an exhibit, and production scale to confirm FbD performance. This phase is carried out in an industrial setting to guarantee that the performed drug product optimization study is reliable and reproducible. The entire process results in a thorough grasp of the product and process at the production and/or commercial scale, in addition to the final product being made available in an "optimized" form compatible with product excellence and federal compliance. A comprehensive and adaptable "control plan" is painstakingly developed and put into practice, ultimately leading to the objective of "continuous improvement" of drug delivery.
