Selective formation of coamorphous systems with enzalutamide: Benzene rings as key structural features
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F25%3A43932416" target="_blank" >RIV/60461373:22340/25:43932416 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.ejps.2025.107281" target="_blank" >https://doi.org/10.1016/j.ejps.2025.107281</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ejps.2025.107281" target="_blank" >10.1016/j.ejps.2025.107281</a>
Alternative languages
Result language
angličtina
Original language name
Selective formation of coamorphous systems with enzalutamide: Benzene rings as key structural features
Original language description
Enzalutamide (ENZ), a non-steroidal antiandrogen used in the treatment of metastatic castration-resistant prostate cancer, exhibits poor aqueous solubility and bioavailability. Coamorphous systems, formed between an active pharmaceutical ingredient (API) and a low-molecular-weight coformer, offer a promising strategy to enhance solubility and dissolution. Here, we systematically screened a range of small organic acids and amino acids as coformers for coamorphous system formation with ENZ. Interestingly, full coamorphous systems formed exclusively with coformers containing a benzene ring, including benzoic acid, salicylic acid, 2-aminobenzoic acid, 2,5-dihydroxybenzoic acid (25H), L-phenylalanine, and L-tryptophan. Crystal structure analysis revealed that ENZ is stabilized in its crystalline state through strong pi-pi stacking, but these interactions are weakened or disrupted upon amorphization. Coamorphization is facilitated by coformers that can stabilize the amorphous phase through molecular complementarity and favorable packing. FTIR indicated limited new strong interactions, suggesting stabilization mainly via molecular mixing and weak pi-pi contacts. Thermal analysis confirmed single-phase systems with distinct Tg values, and stability studies revealed that the ENZ-25H system remained amorphous for nearly four months, outperforming others. Dissolution testing demonstrated up to a 3.6fold increase in intrinsic dissolution rate compared with crystalline ENZ. These results identify aromaticity as a critical structural feature for coamorphous formation with ENZ and provide a rational basis for coformer selection for this drug and, by extension, other aromatic-rich, poorly soluble APIs.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/EH22_008%2F0004607" target="_blank" >EH22_008/0004607: New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
ISSN
0928-0987
e-ISSN
1879-0720
Volume of the periodical
214
Issue of the periodical within the volume
214
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
9
Pages from-to
nestránkováno
UT code for WoS article
001586706800004
EID of the result in the Scopus database
2-s2.0-105017170012