In this study, the possibility of utilising in situ crystalline-to-amorphous transformation for the delivery of poorly water soluble drugs was investigated. Compacts of physical mixtures of γ-indomethacin (IMC) and Eudragit® E in 3:1, 1:1 and 1:3 (w/w) ratios were subjected to dissolution testing at pH 6.8 at which IMC but not the polymer is soluble. Compacts changed their colour from white to yellow indicating amorphisation of IMC. X-ray powder diffractometry (XRPD) confirmed the amorphisation and only one glass transition temperature was observed (58.1 °C, 54.4 °C, and 50.1 °C for the 3:1, 1:1 and 1:3 (w/w) drug-to-polymer ratios, respectively). Furthermore, principal component analysis of infrared spectra resulted in clustering of in situ transformed samples together with quench cooled glass solutions for each respective ratio. Subsequent dissolution testing of in situ transformed samples at pH 4.1, at which the polymer is soluble but not IMC, led to a higher dissolution rate than for quench cooled glass solution at 3:1 and 1:1 ratios, but not for the 1:3 ratio. This study showed that crystalline drug can be transformed into amorphous material in situ in the presence of a polymer, leading to the possibility of administering drugs in the amorphous state without physical instability problems during storage.