Co-amorphization has been utilized to improve the physical stability of the respective neat amorphous drugs. However, physical stability of co-amorphous systems is mostly investigated under dry conditions, leaving the potential influence of moisture on storage stability unclear. In this study, carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios from 3:1 to 1:3 were investigated under non-dry conditions at two temperatures, i.e., 25 °C 55 %RH and 40 °C 55 %RH. Under these conditions, the highest physical stability of CAR-ASP systems was observed at the 1:1 M ratio. This finding differed from the optimal molar ratio previously obtained under dry conditions (CAR-ASP 1:1.5). Molecular interactions between CAR and ASP were affected by moisture, and salt disproportionation occurred during storage. Morphological differences of systems at different molar ratios could be observed already after one week of storage. Furthermore, variable temperature X-ray powder diffraction measurements showed that excess CAR or excess ASP, existing in the binary systems, resulted in a faster recrystallization compared to equimolar system. Overall, this study emphasizes the influence of moisture on co-amorphous systems during storage, and provides options to determine the optimal ratio of co-amorphous systems in presence of moisture at comparatively short storage times.
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