(Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior

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Standard

(Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior. / Holzapfel, Katharina; Liu, Jingwen; Rades, Thomas; Leopold, Claudia S.

In: International Journal of Pharmaceutics, Vol. 616, 121552, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Holzapfel, K, Liu, J, Rades, T & Leopold, CS 2022, '(Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior', International Journal of Pharmaceutics, vol. 616, 121552. https://doi.org/10.1016/j.ijpharm.2022.121552

APA

Holzapfel, K., Liu, J., Rades, T., & Leopold, C. S. (2022). (Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior. International Journal of Pharmaceutics, 616, [121552]. https://doi.org/10.1016/j.ijpharm.2022.121552

Vancouver

Holzapfel K, Liu J, Rades T, Leopold CS. (Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior. International Journal of Pharmaceutics. 2022;616. 121552. https://doi.org/10.1016/j.ijpharm.2022.121552

Author

Holzapfel, Katharina ; Liu, Jingwen ; Rades, Thomas ; Leopold, Claudia S. / (Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior. In: International Journal of Pharmaceutics. 2022 ; Vol. 616.

Bibtex

@article{4e72f6bd0244453fbf4bd77d49d714ae,
title = "(Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior",
abstract = "A novel approach for improvement of the aqueous solubility of poorly water soluble compounds applying co-amorphous systems was investigated by application of the enantiomers of the chiral amino acid tryptophan (TRP) as the model system. (Co-)amorphization of various forms of crystalline TRP was achieved by ball milling. Solid state analysis demonstrated significant differences in the amorphization tendency and physical stability between the two TRP enantiomers alone, the TRP racemate and an equimolar physical mixture of D- and L-TRP (TRP conglomerate). Ball milling for 6 h was required to obtain fully amorphous plain D- and L-TRP, whereas the TRP racemate and the TRP conglomerate were transformed into their amorphous forms already within 90 and 60 min of ball milling, respectively. Physical stability of the co-amorphous TRP conglomerate was observed for up to 60 d at ambient conditions as well as 40 °C/0 % RH. In contrast, the amorphous TRP racemate showed a reduced physical stability under ambient conditions. Interestingly, the intrinsic dissolution rates of the amorphous TRP conglomerate and racemate were not higher than those of the respective crystalline forms. In conclusion, applying two enantiomers of a chiral compound may be a promising approach for fast amorphization of an API and for improving the physical stability of the resulting amorphous form.",
keywords = "Amino acid, Co-amorphization, Conglomerate, Enantiomer, Intrinsic dissolution rate, Physical stability, Racemate",
author = "Katharina Holzapfel and Jingwen Liu and Thomas Rades and Leopold, {Claudia S.}",
note = "Funding Information: The authors would like to thank Isabelle Nevoigt and Claudia Wontorra for performing XRPD measurements. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",
year = "2022",
doi = "10.1016/j.ijpharm.2022.121552",
language = "English",
volume = "616",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - (Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior

AU - Holzapfel, Katharina

AU - Liu, Jingwen

AU - Rades, Thomas

AU - Leopold, Claudia S.

N1 - Funding Information: The authors would like to thank Isabelle Nevoigt and Claudia Wontorra for performing XRPD measurements. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022

Y1 - 2022

N2 - A novel approach for improvement of the aqueous solubility of poorly water soluble compounds applying co-amorphous systems was investigated by application of the enantiomers of the chiral amino acid tryptophan (TRP) as the model system. (Co-)amorphization of various forms of crystalline TRP was achieved by ball milling. Solid state analysis demonstrated significant differences in the amorphization tendency and physical stability between the two TRP enantiomers alone, the TRP racemate and an equimolar physical mixture of D- and L-TRP (TRP conglomerate). Ball milling for 6 h was required to obtain fully amorphous plain D- and L-TRP, whereas the TRP racemate and the TRP conglomerate were transformed into their amorphous forms already within 90 and 60 min of ball milling, respectively. Physical stability of the co-amorphous TRP conglomerate was observed for up to 60 d at ambient conditions as well as 40 °C/0 % RH. In contrast, the amorphous TRP racemate showed a reduced physical stability under ambient conditions. Interestingly, the intrinsic dissolution rates of the amorphous TRP conglomerate and racemate were not higher than those of the respective crystalline forms. In conclusion, applying two enantiomers of a chiral compound may be a promising approach for fast amorphization of an API and for improving the physical stability of the resulting amorphous form.

AB - A novel approach for improvement of the aqueous solubility of poorly water soluble compounds applying co-amorphous systems was investigated by application of the enantiomers of the chiral amino acid tryptophan (TRP) as the model system. (Co-)amorphization of various forms of crystalline TRP was achieved by ball milling. Solid state analysis demonstrated significant differences in the amorphization tendency and physical stability between the two TRP enantiomers alone, the TRP racemate and an equimolar physical mixture of D- and L-TRP (TRP conglomerate). Ball milling for 6 h was required to obtain fully amorphous plain D- and L-TRP, whereas the TRP racemate and the TRP conglomerate were transformed into their amorphous forms already within 90 and 60 min of ball milling, respectively. Physical stability of the co-amorphous TRP conglomerate was observed for up to 60 d at ambient conditions as well as 40 °C/0 % RH. In contrast, the amorphous TRP racemate showed a reduced physical stability under ambient conditions. Interestingly, the intrinsic dissolution rates of the amorphous TRP conglomerate and racemate were not higher than those of the respective crystalline forms. In conclusion, applying two enantiomers of a chiral compound may be a promising approach for fast amorphization of an API and for improving the physical stability of the resulting amorphous form.

KW - Amino acid

KW - Co-amorphization

KW - Conglomerate

KW - Enantiomer

KW - Intrinsic dissolution rate

KW - Physical stability

KW - Racemate

U2 - 10.1016/j.ijpharm.2022.121552

DO - 10.1016/j.ijpharm.2022.121552

M3 - Journal article

C2 - 35131351

AN - SCOPUS:85124195400

VL - 616

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

M1 - 121552

ER -

ID: 299413001