Spray　drying　of　poorly　water-soluble　drugs　in　organic　solvents　is　a　mature　process　in　the　preparation　of　drugs　amorphous　solids　dispersions　(ASDs).　The　use　of　organic　solvents　is　under　increasing　environmental　protection　and　safety　pressure　and　restricts　the　application　of　advanced　polymers　as　proteins　which　are　usually　insoluble　and　unstable　in　organic　solvents.　Aqueous　solution　spray　drying　technology　is　a　candidate　method　for　preparing　ASDs　without　the　use　of　organic　solvents.　Increasing　temperature　and　adding　volatile　additives　can　improve　the　solubility　of　poorly　water-soluble　drugs　in　water　without　introducing　additional　components　and　energy　needed.　In　this　work,　ammonia　assisted　aqueous　solution　spray　drying　method　was　successfully　used　to　prepare　various　ASDs　of　indomethacin　(25%)　with　synthetic　polymers　as　polyvinylpyrrolidone　and　proteins　as　β-lactoglobulin,　lactalbumin　hydrolysate,　bovine　serum　albumin,　with　high　yields,　special　micro　golfs　morphology,　precise　compositions　and　longtime　stabilities,　compared　to　high-temperature　aqueous　solution　spray　drying　method.　ASDs　with　lactalbumin　hydrolysate　and　bovine　serum　albumin　show　better　dissolution　profiles　than　other　ASDs.　Aqueous　solution　spray　drying　is　easily　extended　to　prepare　the　ASDs　of　sulfamerazine　and　celecoxib,　providing　a　possibility　to　avoid　the　use　of　organic　solvents　in　advanced　ASDs　preparations　via　spray　drying.　©　2025　by　the　authors.