Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug-excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy (FT-IR) and x-ray powder diffraction (XRPD) analyses were also realized. The results showed that ACV only exhibited interaction that could influence the stability of the product in the binary mixtures of ACV/magnesium stearate.