The stability of the active pharmaceutical ingredients (API) and the final product is one of the most important factors in the design and development of drug forms. The storage conditions stated on the product label arise from the evaluation of the scientific data extracted from stability studies. In this study, the effect of ointment base excipients on stability was conducted, besides the effect of freeze-thaw tests on product stability. Dexketoprofen trometamol which is a highly soluble active substance in the water was selected as a model drug within the scope of this study. It was formulated as a semi-solid dosage form with different types of bases (an oil-based, a water-based, and emulsion-based ointment excipients). The stability tests in long-term and accelerated conditions were performed on each product at certain periods. The commercial product of dexketoprofen trometamol (Dexalgin gel) was also evaluated. The loss of API in the ointment with high oil content was higher than the others in both long term and accelerated stability test conditions. The active ingredient loss was higher than 5% even after the first freeze-thaw process for all formulation including commercial product in gel form. After two cycle-freeze-thaw processes, the amount of API was dramatically changed (from 18% of degradation in even commercial gel products, which were the most stable formulation in this study). It was presented that freeze-thaw processes were much more crucial than the two month storage in high temperatures (i.e. 40 degrees C).