Comprehensive knowledge of the critical properties of the active pharmaceutical ingredients is a requirement within the modern concept of quality. Praziquantel hemihydrate (HH) and monohydrate (MH) are new solid forms of this antihelmintic agent, which have better solubility properties than the commercial anhydrous solid form (polymorph A). The thermal stability of the hydrates was evaluated, aiming to understand any possible transformation (amorphization, change to a less soluble form). Therefore, HH and MH were prepared along with the related anhydrous solid forms A and B, and characterized employing solid-state nuclear magnetic resonance, powder X-ray diffraction, mid and near infrared spectroscopy, thermal methods and the intrinsic dissolution rate. The transformations of HH and MH under thermal stress conditions were monitored through a variable temperature infrared spectroscopy approach, assisted by multivariate curve resolution with alternating least squares (MCR-ALS), finding that HH undergoes a two-step transformation (HH→B→A) to form A, whereas MH dehydrates directly into form A. This was further confirmed by conventional calorimetric methods (differential scanning calorimetry and thermogravimetry) and powder X-ray diffractometry. The impact of changes in the stressed solid forms and their dissolution rates was also assessed. Significant differences in dissolution performance were found regarding the solid forms produced as a consequence of thermally-induced dehydration.Fil: Salazar Rojas, Duvernis. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área de Análisis de Medicamentos. Instituto de Química Rosario (IQUIR-CONICET); Argentina.Fil: Kaufman, Teodoro Saúl. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área de Análisis de Medicamentos. Instituto de Química Rosario (IQUIR-CONICET); Argentina.Fil: Maggio, Rubén Mariano. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área de Análisis de Medicamentos. Instituto de Química Rosario (IQUIR-CONICET); Argentina.