Effects of polymer addition on the non-strongly interacting binary co-amorphous system carvedilol-tryptophan
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Effects of polymer addition on the non-strongly interacting binary co-amorphous system carvedilol-tryptophan. / Wang, Yixuan; Grohganz, Holger; Rades, Thomas.
I: International Journal of Pharmaceutics, Bind 617, 121625, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Effects of polymer addition on the non-strongly interacting binary co-amorphous system carvedilol-tryptophan
AU - Wang, Yixuan
AU - Grohganz, Holger
AU - Rades, Thomas
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Co-amorphous systems have been developed to address the solubility challenge of poorly water-soluble crystalline drugs. However, due to the thermodynamic instability of amorphous forms, amorphization may result in recrystallization during manufacturing, storage, or dissolution, which is one of the main challenges in the pharmaceutical development of amorphous systems. This could also be the case in some co-amorphous systems with only non-strong interactions between the drug and the co-former (such as hydrogen bond formation and π-π interactions). In this study, a small amount of polymer was added to the binary co-amorphous mixture carvedilol (CAR) - tryptophan (TRP) at a molar ratio of 1:1 and subjected to mechanical activation by ball milling to produce amorphous systems, in order to investigate the effect of co-formulated polymer on the physical properties (solubility, stability, etc.) of non-strongly interacting binary co-amorphous mixtures. After co-formulating polymer to the binary co-amorphous system, stronger interactions were found between CAR and polymer than between CAR and TRP in the ternary polymer containing co-amorphous systems. Compared to the corresponding binary co-amorphous systems, larger areas under the dissolution curves were achieved, indicating an improvement in dissolution behaviour due to a more gradual increase in dissolved drug concentration and a longer period of maintaining drug supersaturation. There was no negative effect of polymer addition on physical stability at room temperature under dry storage conditions for 6 months. Therefore, it is possible to design ternary co-amorphous drug delivery systems with optimized dissolution characteristics by adding a small amount of polymer into co-amorphous binary systems.
AB - Co-amorphous systems have been developed to address the solubility challenge of poorly water-soluble crystalline drugs. However, due to the thermodynamic instability of amorphous forms, amorphization may result in recrystallization during manufacturing, storage, or dissolution, which is one of the main challenges in the pharmaceutical development of amorphous systems. This could also be the case in some co-amorphous systems with only non-strong interactions between the drug and the co-former (such as hydrogen bond formation and π-π interactions). In this study, a small amount of polymer was added to the binary co-amorphous mixture carvedilol (CAR) - tryptophan (TRP) at a molar ratio of 1:1 and subjected to mechanical activation by ball milling to produce amorphous systems, in order to investigate the effect of co-formulated polymer on the physical properties (solubility, stability, etc.) of non-strongly interacting binary co-amorphous mixtures. After co-formulating polymer to the binary co-amorphous system, stronger interactions were found between CAR and polymer than between CAR and TRP in the ternary polymer containing co-amorphous systems. Compared to the corresponding binary co-amorphous systems, larger areas under the dissolution curves were achieved, indicating an improvement in dissolution behaviour due to a more gradual increase in dissolved drug concentration and a longer period of maintaining drug supersaturation. There was no negative effect of polymer addition on physical stability at room temperature under dry storage conditions for 6 months. Therefore, it is possible to design ternary co-amorphous drug delivery systems with optimized dissolution characteristics by adding a small amount of polymer into co-amorphous binary systems.
KW - Amorphization
KW - Dissolution
KW - Molecular interaction
KW - Physical stability
KW - Polymer
KW - Poorly water-soluble drugs
U2 - 10.1016/j.ijpharm.2022.121625
DO - 10.1016/j.ijpharm.2022.121625
M3 - Journal article
C2 - 35259442
AN - SCOPUS:85126098584
VL - 617
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 121625
ER -
ID: 302372927