Comparison of co-former performance in co-amorphous formulations: Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers

Research output: Contribution to journalJournal articleResearchpeer-review

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Comparison of co-former performance in co-amorphous formulations : Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers. / Wu, Wenqi; Grohganz, Holger; Rades, Thomas; Loebmann, Korbinian.

In: European Journal of Pharmaceutical Sciences, Vol. 156, 105582, 2021.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Wu, W, Grohganz, H, Rades, T & Loebmann, K 2021, 'Comparison of co-former performance in co-amorphous formulations: Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers', European Journal of Pharmaceutical Sciences, vol. 156, 105582. https://doi.org/10.1016/j.ejps.2020.105582

APA

Wu, W., Grohganz, H., Rades, T., & Loebmann, K. (2021). Comparison of co-former performance in co-amorphous formulations: Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers. European Journal of Pharmaceutical Sciences, 156, [105582]. https://doi.org/10.1016/j.ejps.2020.105582

Vancouver

Wu W, Grohganz H, Rades T, Loebmann K. Comparison of co-former performance in co-amorphous formulations: Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers. European Journal of Pharmaceutical Sciences. 2021;156. 105582. https://doi.org/10.1016/j.ejps.2020.105582

Author

Wu, Wenqi ; Grohganz, Holger ; Rades, Thomas ; Loebmann, Korbinian. / Comparison of co-former performance in co-amorphous formulations : Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers. In: European Journal of Pharmaceutical Sciences. 2021 ; Vol. 156.

Bibtex

@article{75f021f5cdb84501a85481ac7479636a,
title = "Comparison of co-former performance in co-amorphous formulations: Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers",
abstract = "Co-amorphous systems have been shown to be a potential approach to address the poor water solubility challenge of many drugs. Various low molecular weight molecules, especially amino acids, have been used as potential co-formers. In this study, the differences between various combinations of amino acid-based systems, i.e. the single amino acids glutamic acid (Glu) and arginine (Arg), their physical mixture, glutamic acid-arginine crystalline and amorphous salts, and the corresponding dipeptides (GluArg, ArgGlu), were investigated. Mebendazole (Meb) was used as the model drug. Pure Meb and Meb-co-former mixtures were ball milled to prepare the co-amorphous samples. The shortest amorphization time upon ball milling (30 min) was found for Meb mixtures with the dipeptides and the Glu.Arg amorphous salt. All other samples became amorphous upon milling for 90 min, except Meb-Glu, where Glu remained partially crystalline. Both, single-phase (Meb-Glu-Arg ternary mixtures) and two-phase amorphous systems (Meb-Arg, Meb-GluArg, Meb-ArgGlu) were obtained for different Meb-co-former mixtures after milling. Whilst all co-formers improved the dissolution rate of Meb in a similar fashion (dissolution rate increased by 3.5 to 5.7-fold with respect to crystalline Meb), the highest stability improvement was observed for Meb-dipeptide systems. Interestingly, even though being a two-phase amorphous system, dipeptides were superior to the other co-formers as they possessed higher physical stability.",
keywords = "WATER-SOLUBLE DRUGS, DISSOLUTION RATE, X-RAY, STABILITY, SYSTEMS, SOLUBILITY, MOBILITY",
author = "Wenqi Wu and Holger Grohganz and Thomas Rades and Korbinian Loebmann",
year = "2021",
doi = "10.1016/j.ejps.2020.105582",
language = "English",
volume = "156",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Comparison of co-former performance in co-amorphous formulations

T2 - Single amino acids, amino acid physical mixtures, amino acid salts and dipeptides as co-formers

AU - Wu, Wenqi

AU - Grohganz, Holger

AU - Rades, Thomas

AU - Loebmann, Korbinian

PY - 2021

Y1 - 2021

N2 - Co-amorphous systems have been shown to be a potential approach to address the poor water solubility challenge of many drugs. Various low molecular weight molecules, especially amino acids, have been used as potential co-formers. In this study, the differences between various combinations of amino acid-based systems, i.e. the single amino acids glutamic acid (Glu) and arginine (Arg), their physical mixture, glutamic acid-arginine crystalline and amorphous salts, and the corresponding dipeptides (GluArg, ArgGlu), were investigated. Mebendazole (Meb) was used as the model drug. Pure Meb and Meb-co-former mixtures were ball milled to prepare the co-amorphous samples. The shortest amorphization time upon ball milling (30 min) was found for Meb mixtures with the dipeptides and the Glu.Arg amorphous salt. All other samples became amorphous upon milling for 90 min, except Meb-Glu, where Glu remained partially crystalline. Both, single-phase (Meb-Glu-Arg ternary mixtures) and two-phase amorphous systems (Meb-Arg, Meb-GluArg, Meb-ArgGlu) were obtained for different Meb-co-former mixtures after milling. Whilst all co-formers improved the dissolution rate of Meb in a similar fashion (dissolution rate increased by 3.5 to 5.7-fold with respect to crystalline Meb), the highest stability improvement was observed for Meb-dipeptide systems. Interestingly, even though being a two-phase amorphous system, dipeptides were superior to the other co-formers as they possessed higher physical stability.

AB - Co-amorphous systems have been shown to be a potential approach to address the poor water solubility challenge of many drugs. Various low molecular weight molecules, especially amino acids, have been used as potential co-formers. In this study, the differences between various combinations of amino acid-based systems, i.e. the single amino acids glutamic acid (Glu) and arginine (Arg), their physical mixture, glutamic acid-arginine crystalline and amorphous salts, and the corresponding dipeptides (GluArg, ArgGlu), were investigated. Mebendazole (Meb) was used as the model drug. Pure Meb and Meb-co-former mixtures were ball milled to prepare the co-amorphous samples. The shortest amorphization time upon ball milling (30 min) was found for Meb mixtures with the dipeptides and the Glu.Arg amorphous salt. All other samples became amorphous upon milling for 90 min, except Meb-Glu, where Glu remained partially crystalline. Both, single-phase (Meb-Glu-Arg ternary mixtures) and two-phase amorphous systems (Meb-Arg, Meb-GluArg, Meb-ArgGlu) were obtained for different Meb-co-former mixtures after milling. Whilst all co-formers improved the dissolution rate of Meb in a similar fashion (dissolution rate increased by 3.5 to 5.7-fold with respect to crystalline Meb), the highest stability improvement was observed for Meb-dipeptide systems. Interestingly, even though being a two-phase amorphous system, dipeptides were superior to the other co-formers as they possessed higher physical stability.

KW - WATER-SOLUBLE DRUGS

KW - DISSOLUTION RATE

KW - X-RAY

KW - STABILITY

KW - SYSTEMS

KW - SOLUBILITY

KW - MOBILITY

U2 - 10.1016/j.ejps.2020.105582

DO - 10.1016/j.ejps.2020.105582

M3 - Journal article

C2 - 33039568

VL - 156

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

M1 - 105582

ER -

ID: 255844621