Amorphization is a commonly used method to enhance the dissolution of poorly water-soluble drug. There are a number of different methods to generate amorphous drug substances such as solvent deposition, co-milling (COM), melt-extrusion, 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 achieve dissolution rate enhancement Both COM and SAS precipitations 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 (XPRD, crystallinity), USP dissolution tester, thermogravimetric (TGA, composition), Fourier-transform infrared spectroscopy (MR, drug-polymer interactions) and differential scanning calorimetry (DSC, glass transition temperature, T-g) analysis. Accelerated physical stability stress tests were also conducted on COM and SAS co-precipitates in open pans at 75%RH and 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 and 40 degrees C. COM powders with PVP contents less than 50 wt% re-crystallized after 7 days of storage at 75% RH and 40 degrees C. The values of Tg as a function of mixture composition were comparable to the ideal Gordon-Taylor equation for SAS co-precipitates. TGA analyses revealed that the compositions of both COM and SAS co-precipitates were consistent with the experimentally designed composition. Amorphous form of IDMC produced by COM and SAS has improved dissolution properties as compared to the crystalline form. However, COM amorphous form is less stable than the SAS amorphous form under the stress test conditions. FTIR also revealed there were interactions between IDMC and PVP in both COM and SAS co-precipitates and PVP may influence the re-crystallization kinetics by preventing the self association of indomethacin molecules. (C) 2012 Elsevier B.V. All rights reserved.