**1. Introduction**

In an endeavour to fight various pathological manifestations, medicaments have been administered via various possible routes [1]. Experimental designs techniques have long been used for the optimization of various processes and the development of smart drug delivery system such as the factorial designs since 1926 [2], the designs for screening since 1946 [3], the central composite designs since 1951 [4], and the mixture designs since 1958 [5]. According to Joseph Juran, most of the quality problems are associated with the way by which a pharmaceutical smart drug delivery was designed. A poorly designed pharmaceutical dosage form will show poor efficacy and safety, no matter how many analyses or tests have been done to check its quality.

The quality by design (QbD) is a systemic approach for the development of pharmaceutical formulations that starts with predefined objectives and emphasizes process and product comprehension and process control, based on quality risk management and sound science [6]. The food and drug administration guidance, such as pharmaceutical product development (ICH Q8), quality risk evaluation (ICH Q9), pharmaceutical quality systems (ICH Q10), the briefly highlighted ICH approach to the achieve quality of product through QbD [7], and development and manufacture of drug substances (ICH Q11) [8]. The QbD based approach will provide scientific understanding and knowledge to support smart drug delivery system development [9]. The prime goals of QbD for pharmaceuticals may include: (a) to attain meaningful product and quality specification; (b) to enhance process ability and reduce product variability; (c) to enhance smart dosage form development and manufacturing efficiencies, and (d) to increase cause-effect investigation and regulatory flexibility [6]. The QbD is used to establish the relationship of product performance with the process and product attributes [7, 10]. The applications of QbD in pharmaceutical smart drug delivery system development is systematic, requiring multivariate experiments employing process analytical technology (PAT) and other experiments to recognize critical quality attributes (CQAs) depend upon risk assessments (RAs) [7].

The smart dosage form design and process development cannot be distinguished since dosage form cannot become a product unaccompanied by a defined process. The production process needs to produce a desired standard product typically requires multiple units operating conditions and operations [11]. The outline has to contain all the factors that require to be contemplated for the design of the process. The process factors which cause a vital impact on the quality of the product if changes are contemplated as the critical process attribute (CPAs). The process factor variability, which causes a vital impact on the critical quality of the ingredients should be controlled and monitored, at all times to make sure the process for the targeted quality [6, 11].
