Purpose <p>Amorphous drug nanoparticles can enhance the oral bioavailability of poorly water-soluble drugs, but rapid particle growth limits their effectiveness and manufacturability. Therefore, the goal of this study was to evaluate how stabilizers influence the stability of amorphous drug nanoparticles in solution.</p> Methods <p>Six structurally diverse drugs with varying glass transition temperatures (T_g) were used as model drugs. Seven commonly used pharmaceutical excipients, including both polymers and surfactants, were tested as stabilizers. Particle growth was monitored using dynamic light scattering across different temperatures. Drug-polymer interactions were analyzed via differential scanning calorimetry and solid-state nuclear magnetic resonance spectroscopy.</p> Results <p>Partitioning stabilizers outperformed non-partitioning stabilizers, effectively stabilized nanoparticles at T &gt; &gt; wet T_g of the drug. In contrast, non-partitioning stabilizers showed performance dependent on both the wet T_gs of the drug and the stabilizer. Strong ionic interactions between the stabilizer and the drug were found to be associated with better particle stability.</p> Conclusions <p>The impact of excipients was dependent on their mechanism of action. HPMCAS was the most effective particle stabilizer among all excipients evaluated, possibly due to its ability to inhibit both Ostwald ripening and coalescence.</p> Graphical Abstract <p></p>