The study examined the efficacy of additives in preventing the crystallization of functional ingredients during the spray-drying process. Spray-drying of a hydrophobic drug from alcohol in the presence of a hydrophilic carrier-forming agent was utilized as a representative scenario, which frequently leads to the crystallization of the main drug component induced by the drying process. Ibuprofen (IBP) and its four congeners were employed as representatives of readily crystallizable hydrophobic pharmaceutical compounds. Disaccharides were intentionally employed as components of the drug carrier to create conditions conducive to crystallization. Ten materials, including the IBP congeners, were investigated for their anti-crystallization properties. The findings indicated that additives with a hydrophobic moiety similar to that of IBP and a carboxylic acid salt moiety effectively prevented IBP and its congeners from crystallizing when the additive content was ≥0.2 g/g-drug during spray-drying and storage at 30 °C over silica gel.