The preparation of nano- and microsuspensions used for long-acting injectables include several advantages, where the ability to control the particle sizes of a drug compound, e.g., wet bead media milling, to obtain a desired release rate, has shown to be highly critical. Limiting factors, making the formulation screening process time-consuming, are both the grindability of a compound to obtain the desired particle size profile as well as the addition of a suitable stabilizer at a sufficient concentration to secure a long-term physical stability. Hence, the deformation properties of three different model compounds (i.e., cinnarizine, haloperidol, and indomethacin) were investigated in the present study by quantifying fragmentation after tableting followed by the preparation of nano- and microsuspensions with two different stabilizers (polysorbate 20 and poloxamer 188) and concentrations (1, 2, or 4%), as well as bead size (ø 0.5 or 1.0 mm), during processing. It was found that cinnarizine had brittle properties, haloperidol predominantly plastic properties, and indomethacin elastic properties. Distinct particle size profiles, after milling by the dual centrifugation approach, were achieved for the three model compounds, when prepared under the same manufacturing conditions. It was possible to obtain decreased sizes of cinnarizine particles, whereas the grindability for haloperidol was more restricted due to its plastic properties. The study further showed that higher concentrations of poloxamer 188 were needed to obtain smaller sizes of particles when compared to polysorbate 20. Short-term stability studies showed an increase in sizes of particles over 49 days stored at elevated temperatures, especially for indomethacin suspensions stabilized with the highest polysorbate 20 concentration, due to increased solubility from the stabilizer vehicle as confirmed by a solubility study. Sizes of haloperidol particles remained relatively stable when stabilized with the highest concentration of polysorbate 20, even with increased solubility, indicating a higher physical stability as compared to cinnarizine and indomethacin.