Some Items of Interest to Process R&D Chemists and Engineers

Merck scientists shared an example of aligning API process development and product formulation to accelerate the nomination of a robust commercial drug product manufacturing process and to provide early insight into desired API material attributes (Hartmanshenn, C.; et al. J. Pharm. Sci., DOI: 10.1016/j.xphs.2024.11.008). The strategy involved using a diverse range of crystallization conditions and particle size modification technologies to deliberately vary the morphology and density of early API batches along with the particle size distribution ahead of the assessment of their impact on the tensile strength and dissolution of drug product tablets. In the case study described, the very high API loading in the tablets meant that the API material attributes could have an especially large influence on tablet manufacture and performance. The study showed that the API morphology was in fact much less important than the particle size distribution, providing potential flexibility around the API crystallization and how it is described in the marketing authorization application.