Objectives Proposed research deals with the potential application of mechanochemical activation by grinding in the improvement of unfavorable physico-chemical characteristics of Praziquantel, namely in the enhancement of solubility and oral bioavailability of the drug. The focal point of the research is to give detailed insights into degradation products formed during the mechanochemical activation by grinding Praziquantel with and without additives. The studied mechanisms of degradation of Praziquantel in these conditions will give insights into critical parameters of the process. These critical parameters can then be further modified in future research, the selection of additives can be made easier and the potential of mechanochemical activation for enhancement of solubility of insoluble drugs can thus be better utilized. These findings are of importance in the future development of formulations with controlled and targeted release of drugs with low solubility. This can then make the therapeutic effects of insoluble drugs better and therapeutic indications broader. Materials and Methods The data that was used in the research was compiled partially from personal collaborative research on the topic and partly by searching the common databases by the theme that is relevant to the thesis, grading the knowledge from more common to more specialized. All of the gathered data was studied and critically evaluated based on the issues concerning the chemical and photochemical instability of praziquantel during the mechanochemical activation by grinding. Results Mechanochemical activation has been shown as an appropriate method for the preparation of products with enhanced pharmaceutical and biopharmaceutical properties of Praziquantel. Products that can be obtained by the method are new polymorphic forms, polymorphic dispersions, cocrystals and inclusion complexes. These new praziquantel products have the potential to advance anthelmintic therapy. Praziquantel has shown a tendency for degradation when placed under certain conditions. Some of the degradation products that were formed in the conditions of mechanochemical grinding of praziquantel with additives have been identified. The theoretically proposed mechanism of oxidation has been experimentally proven to be catalyzed by light and temperature. The identified degradation products have been tested in silico for their mutagenic/cancerogenic potential, as this an important information when it comes to the safety of application of the products of praziquantel that would be obtained by mechanochemical activation. Conclusions Considering the tendency for oxidative degradation of Praziquantel under certain conditions it is important to take into account the exclusion of light and elevated temperatures when planning future grinding experiments because light and temperature have been presumed theoretically and shown experimentally as the major catalysts in such oxidative degradation pathways. The grinding is done in closed metal, hermetically sealed containers, so the treated samples are by default protected from light. Furthermore, it would be very important to provide some kind of temperature tracking and regulation during the mechanochemical experiments. Cryogenic conditions are probably necessary, but temperatures below room temperature should be considered. The second critical factor is the oxygen itself. In the pharmaceutical industry, many operations is done under the inert atmosphere of nitrogen, the experiments of mechanochemical activations should be redone in an inert atmosphere as well, this can be done by purging the vessels with either nitrogen or argon and then hermetically sealing them for the entire experiment. This kind of future planning of the experiments will give new insights into the mechanism of degradation and will make the development and scale-up of the process of mechanochemical activation possible.