Abstract Ethylene-vinyl acetate (EVA) is widely used as a membrane or matrix for transdermal drug delivery systems. In an attempt to determine the state of a drug in the EVA matrix, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and thermal analysis of the quinupramine–EVA matrix were carried out and the results were compared with those of a physical mixture of quinupramine and EVA at the same ratio. The 1:2 matrix of quinupramine with EVA was prepared using the casting method. The XRD pattern of the quinupramine test preparations revealed that the pure quinupramine was crystalline in nature, whereas the quinupramine in the EVA matrix was an amorphous form, which leads to increased drug release. The FT-IR spectra of quinupramine in the physical mixture showed absorption bands at around 3000–3050 cm −1 whereas these absorption bands were not observed in the quinupramine–EVA matrix. The thermal studies of quinupramine in the physical mixture showed an endothermic peak at 154–156 °C, which is the melting point of the drug, but there was no such endothermic peak observed in the EVA matrix. In conclusion, the physicochemical interactions between quinupramine and EVA, might occur at the molecular level, and that quinupramine was not crystalline in the EVA matrix.