The aim of this work is to develop an environmentally friendly and highly efficient technology that enables the co-crystallization and co-agglomeration of active ingredients or the crystallization of an active ingredient and simultaneous agglomeration with another active ingredient in pure water using oiling out. By creating the phase diagram and utilizing the oil droplets that are formed in an oiling system, spherical co-agglomerates with desired active ingredient ratios, ibuprofen (IBU) with a second active pharmaceutical ingredient (API), including L.-Menthol (MT), Praziquantel (PZQ), Rivaroxaban (RXB) and Lenalidomide (LDM) were successfully made and were simply based on a heat-quenching process. The shaping processes of the spherical co-agglomerates comprised two types of mechanisms: co-oiling-out and single-oiling-out mechanisms, making the oiling-out-co-agglomeration (OOCA) technique suitable for a wide range of applications in pharmacy is. In particular, the co-oiling-out mechanism proposed and designed for the first time in this work based on ternary phase diagrams from (API1–API2– Water), uniform oil droplets were produced by two active ingredients, which guarantee a high level of uniformity in the content in the co-agglomerate products. The OOCA technique developed in this thesis can not only integrate crystallization and granulation into one work unit, but also contribute to the achievement of a combination of active substances (polypills). Through simulation and calculation, an effective drug screening strategy was developed that can be applied to the OOCA technique, greatly reducing the use of chemical substances and saving time in the promotion of OOCA.