A Framework for Efficient Process Development Using Optimal Experimental Designs

Abstract

Introduction The aim of this study was to develop and demonstrate a framework assuring efficient process development using fewer experiments than standard experimental designs. Methods A novel optimality criterion for experimental designs (Iw criterion) is defined that leads to more efficient process development because: (a) prior knowledge is used in the experimental design to focus on optimal processing conditions and (b) a lean design is used which can dramatically reduce the number of experiments compared to standard designs. In this way, the criterion serves as a framework to connect a series of screening and optimization designs. Results The philosophy behind the Iw criterion is explained including a detailed step-wise discussion how to apply it in practice. Moreover, its advantages were shown in an industrial process development case using a screening and an optimization design that were not explicitly connected. In this paper, a reduction of 21% of experiments could be obtained compared to the traditional approach using standard experimental designs and no framework. Conclusions The Iw criterion is a valuable tool to increase accuracy and to speed up research that contain sets of experiments and where prior knowledge is already available or will be derived using screening designs.

Quality by Design: Impact of Product Variables and Their Interaction on the Particle Size in Lyophilization of Sodium Fluoride

“…A 4 3 fractional factorial design ( Table 1) was applied to evaluate the main effects of experiments, Concentration of sodium fluoride, Concentration of polyvinylpyrrolidone, Volume of sample solution, drying surface area [15]. Preliminary experiments were conducted to optimize the lyophilization drying cycle for Sodium fluoride.…”