The aim of this study was to determine the miscibility of drug and excipient to predict if glass solutions are likely to form when drug and excipient are melt extruded. Two poorly water-soluble drugs, indomethacin and lacidipine, were selected along with 11 excipients (polymeric and non-polymeric). Estimation of drug/excipient miscibility was performed using a combination of the Hoy and Hoftzyer/Van Krevelen methods for Hansen solubility parameter calculation. Miscibility was experimentally investigated with differential scanning calorimetry (DSC) and hot stage microscopy (HSM). Studies were performed at drug/excipient ratios, 1:4, 1:1 and 4:1. Analysis of the glass transition temperature (T_g) was performed by quench cooling drug/excipient melts in the DSC. Differences in the drug/excipient solubility parameters of <7.0 MPa^1/2 were predicted to indicate significant miscibility and, therefore, glass solution formation on melt extrusion. In comparison, differences of <10 MPa^1/2 were expected to indicate a lack of miscibility and not form glass solutions when melt extruded. Experimentally, miscibility was shown by changes in drug/excipient melting endotherms and confirmed by HSM investigations. Experimental results were in agreement with solubility parameter predictions. In addition, drug/excipient combinations predicted to be largely immiscible often exhibited more than one T_g upon reheating in the DSC. Melt extrusion of miscible components resulted in amorphous solid solution formation, whereas extrusion of an 'immiscible' component led to amorphous drug dispersed in crystalline excipient. In conclusion, combining calculation of Hansen solubility parameters with thermal analysis of drug/excipient miscibility can be successfully applied to predict formation of glass solutions with melt extrusion.