The physical stability of drugs linked to quality-by-design (QbD) and in-process technology (PAT) perspectives

Abstract

The physical stability of solid-state forms in which drugs may exist is in some sense an overlooked aspect. In an era where strategies such as amorphous solid dispersions or co-amorphous preparations might provide answers to stumbling blocks such as poor drug solubility and bioavailability, the physical stability of such solid-state preparations should be a priority. Furthermore, the pharmaceutical industry is moving towards adapting a real time release of pharmaceutical products strategy, through the utilization of process analytical technology. It is thus becoming imperative to investigate the various types of phase transformations a specific solid-state form of a drug may undergo. Also, to critically assess the applicability of process analytical tools that may be sensitive enough to monitor not only chemical but also physical drug stability. These combined efforts allow quality to be built into the product, rather than dealing with costly post batch release recalls. Given that drug stability is an essential quality attribute for a drug product and the quality-by-design approach (QbD) is a best solution to build quality in all pharmaceutical products we focussed on the critical material attributes (CMAs), specifically relating to the physical stability of any given drug. This review highlights physical drug stability in relation to CMAs and how this ultimately link to the finished pharmaceutical product. Investigated challenges associated current PAT strategies is also discussed.

Keywords: In-process controls; PAT; Pharmaceutical processes; Physical stability; Quality-by-design.