Are traditional small-scale screening methods reliable to predict pharmaceutical spray drying?

Driven by the new trend to build quality into products and reducing empiricism, small-scale screening techniques have been frequently used to evaluate, thermodynamic of drug solubility in the polymer, and drug-polymer kinetic amorphous miscibility. In this paper, these methods have been overviewed to shed light on their liabilities in predicting spray-dried amorphous solid dispersions' (ASDs) properties. By scrutinizing relevant open literature, several inconsistencies have been recognized, deemed to be due to the inability of conventional miniaturized means to simulate the spray drying process operations/constraints in formulating active pharmaceutical ingredients (APIs). Given the complex interplay of thermodynamics of mixing, heat and mass transfer, and fluid dynamics in this process, scaling rules have been introduced to remedy arisen issues in conventional miniaturized tools. Accordingly, spray drying process is analyzed considering the fundamental physical transformations involved, i.e. atomization and drying. Each transformation is explored from a scaling perspective with an emphasis on key response factors, and ways to retain them for each transformation across scales. Prospective bifurcated developments may improve the odds of successful formulations/process conditions later on during development stages.