Development of a Design Space for a Unit Operation: Illustration Using Compression-Mix Blending Process for the Manufacture of a Tablet Dosage Form

Abstract

This paper describes the development of an orthogonal design space for a compression-mix blending unit operation for the manufacture of tablet dosage form using an empirical approach. Potential critical process parameters identified through a risk assessment process were assessed through a full-factorial design of experiment for impact on material attributes and drug product critical quality attributes (DP CQA). The impact on each individual attribute measured as responses were subjected to statistical analysis by analysis of variance and regression models were built on the statistically significant effects (p < 0.05). Design space for relevant DP CQA was created using 95% predicted interval estimates. Orthogonal design space for the unit operation was proposed by overlaying design spaces generated for individual DP CQAs. The resulting orthogonal design space made implementation of manufacturing flexibility in to routine manufacturing process and into control strategy simpler and straightforward.