Effects of polymer addition on the non-strongly interacting binary co-amorphous system carvedilol-tryptophan

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.

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About this article: Yixuan Wang, Holger Grohganz, Thomas Rades, Effects of polymer addition on the non-strongly interacting binary co-amorphous system carvedilol-tryptophan, International Journal of Pharmaceutics, Volume 617, 2022,
121625, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2022.121625. (https://www.sciencedirect.com/science/article/pii/S0378517322001806)

Materials
Carvedilol (CAR, MW = 406.47 g/mol) was purchased from Cipla Ltd. (Mumbai, India); L-tryptophan (TRP, MW = 204.23 g/mol) was used as the co-former and was purchased from Sigma-Aldrich (St. Louis, MO, USA). HPMC (Pharmacoat 603, substitution type 2910, viscosity 3 mPas) was purchased from Shin-Etsu Chemicals Co. (Chiyoda-ku, Tokyo, Japan); PVPVA64 (Kollidon VA 64 Fine) was purchased from BASF North America (Florham Park, New Jersey, USA).