(Co-)amorphization of enantiomers – Investigation of the amorphization process, the physical stability and the dissolution behavior
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(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 journal › Journal article › peer-review
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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