A quality by design (QbD) case study on enteric-coated pellets: Screening of critical variables and establishment of design space at laboratory scale

Abstract

PlacketteBurman designBoxeBehnken design Naproxen Quality by design a b s t r a c tThe study aims to prepare naproxen enteric-coated pellets (NAP-ECPs) by fluid-bed coating using QbD principle. Risk assessment was firstly performed by using failure mode and effect analysis (FMEA) methodology. A PlacketteBurman design was then used for assessment of the most important variables affecting enteric-coated pellets characteristics. A BoxeBehnken design was subsequently used for investigating the main, interactive, and quadratic effects of these variables on the response. By FMEA we discovered that eight factors should be considered to be high/important risk variables as compared with others.The responses of acid resistance and cumulative drug release were taken as critical quality attributes (CQAs). Pareto ranking analyses indicated that the coating weight gain (X 7 ), triethyl citrate percentage (X 1 ) and glycerol monostearate percentage (X 2 ) were the most significant factors affecting the selected responses out of the eight high-risk variables.Optimization with response surface method (RSM) further fully clarified the relationship between X 7 , X 1 , X 2 and CQAs, and design space was established based on the constraints set on the responses. Due to the extreme coincidence of the predicted value generated by model with the observed value, the accuracy and robustness of the model were confirmed.It could be concluded that a promising NAP-ECPs was successfully designed using QbD approach in a laboratory scale.

Development of nanostructured lipid carriers containing salicyclic acid for dermal use based on the Quality by Design method

“…Therefore, the QbD approach is more proactive and refers to a systematic process compared to the mainly empirical methodologies used earlier (Beg, S. et al, 2015, Shah, B. et al, 2015, Xu, X. et al, 2011Xu, X. et al, 2012, Kan, S. et al, 2014, Wang, J. et al, 2015, Kovacs, A et al, 2016. Risk assessment and the Design of Experiments (DoE) techniques within the risk assessment process are key elements of QbD methodology (Fig.1).…”

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“…Acid resistance and cumulative drug release were identified CQAs, based on which design space was established. Confirmation tests showed that the predicted and the response values of the formulations with different variables were similar, thus the validity of the model was established and all the parameters were robust within design space 10 . Coating Process Optimization: Variability in the coating thickness is a common problem during tablet coating; it alters the aesthetics and taste masking properties.…”

Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach

“…(3) identifying, through prior knowledge, experimentation, and risk assessment, the material attributes and process parameters that can have an effect on product CQAs; (4) determining the functional relationships that link material attributes and process parameters to product CQAs through the development of multivariate experiments using Design of Experiments (DoE); (5) establishing a design space, and (6) ensuring continual improvement and innovation throughout the product lifecycle [19,23].…”