Using thermal methods such as thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), we investigated the interactions between the active substance, doxycycline, and excipients, such as kleptose, sodium hydrogen carbonate, ascorbic acid and K2S, which are used in the formulation of pharmaceutical products. Based on the research, we found out which excipients react with the active substance and to what extent this interaction has a stabilizing or destabilizing effect. The structural analysis of the active substance was carried out in order to identify the sample of doxycycline hyclate, using X-ray diffraction on a polycrystalline sample. The obtained data was compared with the crystal structures stored in the crystallographic database. An insight into the crystal structure confirmed that the active substance contains two molecules of doxycycline in the form of a chloride salt and one molecule of water and ethanol. It was found that the formulation containing kleptosa shows a high probability of interaction between doxycycline and cyclodextrin, which could be a consequence of the formation of an inclusion complex. In the case of the formulation with polyvinylpyrrolidone, no changes were observed that would indicate an interaction between doxycycline and the polymer. The addition of sodium hydrogencarbonate to the formulation suggests a possible interaction, which can be realized through cationic interactions or by the reaction of hydrogencarbonate with positively charged parts of the molecules. For the mixture of doxycycline and ascorbic acid, thermal measurements show a high probability of a negative influence of ascorbic acid on the stability of doxycycline, which may lead to the decomposition of the compound or the formation of a new crystalline form. The conducted research confirmed the hypothesis that thermal methods can serve in the selection of excipients suitable for creating formulations, as well as provide key information about potential interactions that can affect the stability and effectiveness of the final pharmaceutical product.