Ball-milling is usually used to prepare co-amorphous drugââ?¬â??amino acid (AA) mixtures.\nIn this study, co-amorphous drugââ?¬â??AA mixtures were produced using spray-drying, a scalable\nindustrially preferred preparation method. The influence of the solvent type and solvent composition\nwas investigated. Mixtures of indomethacin (IND) and each of the three AAs arginine, histidine,\nand lysine were ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was\nperformed at different solvent ratios in (a) ethanol and water mixtures and (b) acetone and water\nmixtures. Different ratios of these solvents were chosen to study the effect of solvent mixtures on\nco-amorphous formulation. Residual crystallinity, thermal properties, salt/partial salt formation,\nand powder dissolution profiles of the INDââ?¬â??AA mixtures were investigated and compared to pure\ncrystalline and amorphous IND. It was found that using spray-drying as a preparation method,\nall INDââ?¬â??AA mixtures could be successfully converted into the respective co-amorphous forms,\nirrespective of the type of solvent used, but depending on the solvent mixture ratios. Both ball-milled\nand spray-dried co-amorphous samples showed an enhanced dissolution rate and maintained\nsupersaturation compared to the crystalline and amorphous IND itself. The spray-dried samples\nresulting in co-amorphous samples were stable for at least seven months of storage.
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