Novel Pharmaceutical Cocrystals of Tegafur: Synthesis, Performance, and Theoretical Studies.
DFT
cocrystal
dissolution
solubility
tegafur
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
30 Jan 2024
30 Jan 2024
Historique:
received:
07
11
2023
accepted:
22
01
2024
medline:
31
1
2024
pubmed:
31
1
2024
entrez:
30
1
2024
Statut:
aheadofprint
Résumé
Tegafur (TF) is one of the most important clinical antitumor drugs with poor water solubility, severely reducing its bioavailability. This work develops new cocrystals to improve the solubility of TF and systematically investigates the intermolecular interactions to provide new insights into the formation of cocrystal and changes in physicochemical properties. In this paper, two new 1:1 cocrystals of TF with 2,4 dihydroxybenzoic acid (2,4HBA) and p-nitrophenol (PNP) were synthesized. The cocrystal products were identified and characterized by various solid state analysis techniques. And the high performance liquid chromatography (HPLC) was conducted to determine the solubility and dissolution rate of TF and cocrystals. Moreover, the quantum chemistry calculations of crystal structure provided theoretical support for the results. Compared with pure TF, the solubility and dissolution rate of TF-2,4HBA is significantly increased in a pH 6.8 buffer at 37°C. Under accelerated storage conditions (40°C, 75% RH), all cocrystal exhibits excellent stability over 8 weeks. Hirshfeld surface (HS) analysis, atoms in molecules (AIM) analysis, interaction region indicator (IRI) analysis, molecular electrostatic potential surface (MEPS) analysis and frontier molecular orbital (HOMO-LUMO) analysis were integrated to understand the hydrogen bonding interaction more comprehensively. The simulation results are in good agreement with the experimental data. The results show that the analysis of physical and chemical properties of TF-PNP cocrystal and TF crystal by quantum chemistry method is reliable at molecular level. These results are helpful to provide guiding methods in the cocrystal development and theoretical study of tegafur.
Identifiants
pubmed: 38291166
doi: 10.1007/s11095-024-03668-4
pii: 10.1007/s11095-024-03668-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 21978201
Organisme : National Natural Science Foundation of China
ID : 22108196
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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