Formulation by Design: An Overview

*Ushasi Das, Dilip Kumar Panda and Sanchita Mandal*

## **Abstract**

Quality is the most important and necessary attribute for pharmaceutical product development, and it has become the focus of regulatory bodies in order to approve safe, efficacious, stable, patient-compliance, and cost-effective drug delivery systems. QbD-based formulation development is discovered to be an immerging technique in this context. FbD is a formulation development concept that aims to create more effective, safe, robust, cost-effective, and patient-compliant drug delivery systems. This chapter will provide an overview of Formulation by Design (FbD), different terminologies, design of experiment (DoE) and quality by design (QbD), types of experimental design, QbD applications, and FbD methodology along with benefits.

**Keywords:** formulation by design (FbD), quality by design (Qbd), Design of Experiment (DoE), drug delivery systems, pharmaceutical product development

### **1. Introduction**

Quality is the most crucial and essential attribute for pharmaceutical product development, and it has become the thrust area for the regulatory bodies to approve safe, efficacious, stable, patient-compliance and economical drug delivery systems. It is important to recognize that "The Quality cannot be tested into products; i.e., quality should be build in by design". In this context, QbD-based formulation development is found to be an immerging technique. Pharmaceutical cGMPs for the 21st Century - A Risk-Based Approach, published in 2004, describes the Quality by Design approach, which was approved by the FDA. Detailed specifications for pharmaceutical product quality are provided in International Conference on Harmonization (ICH) Q8 pharmaceutical development, Q9 quality risk assessment, and Q10 pharmaceutical quality system. QbD and DoE strategies aid in the implementation of ICH/Q8 and ICH/Q9 [1]. Pharmaceutical Quality by Design (QbD) begins the systematic development of product(s) and process(es) with desired quality based on the Juran's Quality philosophy. The QbD philosophy, which is a patient-centric approach, prioritizes patient safety by designing drug products with enhanced quality and decreased manufacturing costs by planning quality early to prevent quality crises [2]. ICH guidance Q8 (R2) describes QbD as, "a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and

process control, based on sound science and quality risk management" [3]. Quality by design is an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines. The identification, justification, and management of all sources of variability impacting a process are some of the objectives of quality by design. This enables the finished medicine to consistently meet its predefined characteristics from the start - so that it is 'right first time' [4]. The OFAT-method (onefactor-at-a-time) was the conventional strategy for ensuring and sustaining product quality. It was an empirical technique based on trial and error and built on the *ceteris paribus* principle. This method included the risk of accounting for the potential occurrence of unanticipated, out-of-specification results due to inadequate product and process understanding, both during process optimization and at the validation stage [5]. In these OVAT experiments, the first variable is fixed at a specified value, and each subsequent variable is investigated until no more improvement in the response variable is shown (s). In a summary, the OVAT technique has shown to be insignificant in terms of effort, time, and money as well as unable to offer the true answer by correcting the errors; the results continue to be unpredictable and sometimes even unsuccessful [6]. Recently, whether in industrial practice or in the research milieu, a comprehensive and rigorous approach of pharmaceutical quality by design (QbD) has become popular throughout drug product development [3, 6–9]. **Table 1** provides a brief representation of the advantages of FbD over OVAT methodology. DoE along with QbD having much wider applicability in recent trends in the Pharma industrial as well as in the research milieu, an appropriate term has evolved specifically in development of pharmaceutical dosage form, that is, "Formulation by Design (FbD)". The FbD methodology, therefore, tends to encompass in its purview a rational usage of DoE approach to design more efficacious, safe, robust, economical and patient-compliant Drug Delivery System to accomplish the QbD objectives. The FbD technique is remarkable for its ability to forecast formulation performance as well as


**Table 1.**

*Comparison of OVAT (one-factor-at-a-time) and FbD (formulation by design) methodology.*

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

identify and calculate potential interactions and synergy between variables. FbD helps to fully comprehend the formulation system, and can trace and rectify a "problem" in a remarkably easier manner. As a result, the FbD technique frequently includes a reasonable application of the DoE approach to create high-quality drug products in an efficient and economical manner, endeavoring ultimately to achieve the QbD objectives [10].
