The feasibility of the Depressurization of an Expanded Liquid Organic Solution (DELOS) method to process different active pharmaceutical ingredients (APIs) as finely divided powders with narrow particle size distribution, high crystallinity degree, high polymorphic purity, and free from residual solvent has been demonstrated. Cholesterol, acetylsalicylic acid (aspirin), naproxen, acetaminophen, and ibuprofen were chosen as model drugs. It has been demonstrated that the supersaturation ratio attained during crystallization from CO 2-expanded solvents can be modulated through appropriate variations of process parameters - CO 2 content and concentration of the initial solution. In view of the potential application that compressed fluids-based technologies have in the pharmaceutical industry, a preliminary scalability study of the process in compliance with the constraints imposed by the Good Manufacturing Practices (GMP) specifications is presented herein. © 2012 American Chemical Society.