The conformational flexibility of organic molecules introduces more structural options for crystallization to occur but has potential complications, such as, reduced crystallization tendency and conformational polymorphism. Although a variety of energetically similar conformers could be anticipated, it is extremely difficult to predict the crystal conformation for conformationally flexible molecules. The present study investigates differences in thermodynamic parameters for the free base, c-FB, and an amorphous dihydrochloride salt, a-Di-HCl, of a conformationally flexible drug substance, tenapanor (RDX5791). A variety of complementary techniques such as, thermal analysis, powder X-ray diffraction (PXRD), and molecular modeling were used to assess the thermodynamic properties and the propensity of crystallization for a-FB and a-Di-HCl, tenapanor. Molecular modeling and total scattering measurements suggested that the a-Di-HCl salt exists in an open elongated state with local 1D stacking, which extends only to the first nearest neighbor, while the a-FB shows local stacking extending to the third nearest neighbor. The overall relaxation behavior, which typically is an indicator for physical stability, as measured by modulated temperature differential scanning calorimetry and PXRD suggested a nontypical dual relaxation process for the dihydrochloride salt form. The first relaxation was fast and occurred on warming from the quench conditions without any thermal annealing, while the second relaxation step followed a more traditional glass relaxation model, exhibiting an infinite relaxation time. Similar analysis for the a-FB suggested a comparatively shorter relaxation time (about 19 days) that results in its rapid crystallization. This observation is further validated with the extensive amount of physical stability data collected for the a-Di-HCl salt form of tenapanor under accelerated and stress stability conditions, as well as long-term storage for more than 3 years that show no change in its amorphous state.