Structured development approach for amorphous systems

Abstract

A structured development approach is presented to guide the development of stable and commercially viable polymer based amorphous formulations. The proposed approach should not only enable the delivery of poorly soluble drugs but also help to reduce the API needs, reduce in vivo screening, minimize risks for late-stage development, and should ensure consistent quality. During initial assessment, a guided evaluation of the physicochemical properties of the API helps to assess the degree of difficulty for the development. A range of tests including in silico evaluation, high-throughput screening assays, and miniaturized screening tools provide a road map for selecting the appropriate polymer, drug loading, and suitable manufacturing process. A dedicated section provides a review of the characterization tools to assess and quantify the crystallinity, understanding the phase behavior of amorphous solid dispersions, and designing the in vitro dissolution methods. Finally, a reference chart is provided that summarizes the key concepts proposed as part of the structured development approach that can serve as a blueprint for the development of amorphous formulations. The current authors would like to thank and acknowledge the significant contribution of the previous authors of this chapter from the first edition. This current second edition chapter is a revision and update of the original authors’ work.