Recently, amorphization methods are used to enhance the dissolution of poorly water-soluble drugs. There are a number of different methods to generate amorphous drug substances such as solvent deposition, co-milling (COM), spray-drying, melt-quenching and supercritical fluids technology. In this study, the effectiveness of a low-cost and easily scalable process COM was compared with the high-cost and precision-controlled supercritical anti-solvent (SAS) process to amorphize indomethacin (IDMC) with a water-soluble polymer excipient poly(vinylpyrrolidone) (PVP) to improve the physical stability of the IDMC amorphous form. Both COM and SAS precipitation were conducted at IDMC to PVP ratios of 60:40, 50:50 and 20:80. The untreated COM and SAS powders (before and after storage) were characterized using scanning electron microscopy (SEM, morphology), X-ray powder diffractometry (XRD, crystallinity), thermogravimetric analysis (TGA, composition), gravimetric vapour sorption (GVS, moisture isotherms), Fourier-transform infrared spectroscopy (FTIR, drug polymer interactions), inverse gas chromatography (IGC, surface energetic and structural relaxations) and Raman mapping (RM, spatial distribution). Accelerated physical stability stress tests were also conducted on COM and SAS co-precipitates in open pans at 75%RH/40 degrees C in order to evaluate their physical stability. SAS co-precipitates with PVP contents more than 40 wt.% were X-ray amorphous form and remained stable after more than 6 months of storage at 75%RH/40 degrees C. COM powders with PVP contents less than 50 wt.% re-crystallized after 7 days of storage at 75%RH/40 degrees C. FTIR spectra suggested that hydrogen bonding formed between PVP amide carbonyl and IDMC carboxylic acid hydroxyl groups for all COM and SAS co-precipitates. Therefore, the amorphous phase present in COM and SAS co-precipitates could be stabilized by the intermolecular hydrogen bonds between IDMC and PVP which improved its physical stability against re-crystallization. IGC studies also revealed that different preparation methods used to generate the amorphous form have an effect on its physical stability in terms of surface structural relaxation as well as having different surface energetics. Overall the surface structural relaxation of SAS co-precipitate was slower than COM samples indicating that SAS co-precipitate was physically more stable than COM sample. Finally, this work has demonstrated the potential of using PVP as a suitable "amorphous inducing and stabilizing" agent for a poorly water-soluble drug such as IDMC using co-milling and SAS processes. (C) 2013 Elsevier B.V. All rights reserved.