A Review on AI-Enabled Formulation 4.0: A Predictive Modelling Framework Next- Generation Nanomedicine Development

The conventional paradigm of nano formulation development the heuristic approaches, low-throughput, and trial-and-error paradigm is a fundamental bottleneck to clinical translation of nanomedicines. The present review offers the proposal of the transformative, predictive framework called Formulation 4.0 which is a synthesis of regulatory-scientific principles of Quality by Design (QbD), predictive abilities of Artificial Intelligence/Machine Learning (AI/ML), and the simulative dynamics of Digital Twins. We critically review how AI/ML has been applied to decipher the complicated relationship between material characteristics, process variables, and critical quality attributes (CQAs) and specifically, to predict particle size, optimization of solvent / antisolvent systems, and predict stability. The cyber-physical infrastructure of this new paradigm is introduced as the cloudbased smart formulation lab where the high-throughput experimentation supplies continuously updated digital twins that are optimized in silico and scale-up. Last but not the least, we discuss key issues regarding the changing role of experimentation, and the new ethical, intellectual property, and regulatory concerns of this data-driven future. Curing some of the current discoveries in AI in the field of nanomedicine, this review provides a future direction of pre-rational, efficient, and predictive pharmaceutical development.