The influence of moisture on the storage stability of co-amorphous systems
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The influence of moisture on the storage stability of co-amorphous systems. / Liu, Jingwen; Rades, Thomas; Grohganz, Holger.
In: International Journal of Pharmaceutics, Vol. 605, 120802, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The influence of moisture on the storage stability of co-amorphous systems
AU - Liu, Jingwen
AU - Rades, Thomas
AU - Grohganz, Holger
N1 - Publisher Copyright: © 2021 The Author(s)
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Co-amorphous
KW - Moisture
KW - Molar ratio
KW - Physical stability
KW - Recrystallization
U2 - 10.1016/j.ijpharm.2021.120802
DO - 10.1016/j.ijpharm.2021.120802
M3 - Journal article
C2 - 34144131
AN - SCOPUS:85108287744
VL - 605
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 120802
ER -
ID: 273633882