Self-assembly of antifungal agent 5-fluorocytosine and nutrient trans-p-coumaric acid furnishes a cocrystal with the potential to reduce toxicity and side effects for the drug: a case study combining theory with experiment

Abstract

The current work aims to take full advantage of the structural superiority and hepatoprotective effect of nutriment trans-p-coumaric acid (TPCA) to decrease the solubility and dissolution rate of antimycotic agent...

Supramolecular self-assembly with p-coumaric acid offers the first cocrystal for perfecting the physicochemical peculiarity and enhancing the antifungal effect of drug bifonazole

“…Evidently, the melting point is lower than that of BFZ (152.4 °C) and TPA (211.5 °C), 58,59 revealing the occurrence of a novel crystalline phase. Without a doubt, the reduced weight in the red TG curve at the same position can also confirm the occurrence of a novel phase, because the mass loss displays that the initial decomposition almost coincides with the onset of an endothermic peak, 36 and then it loses weight quickly after it reaches the melting point, further offering additional proof of the cocrystal generation. Furthermore, the weight of the cocrystal does not suffer from any reduction in the TG curve prior to the melting point, illustrating that there is no existence of the solvent molecule in the cocrystal, in keeping with the SCXRD analysis above.…”

“…In particular, the brighter and larger the red circles are, the stronger the intermolecular interactions are, and the converse is also true. 36 From the comparison, it's easy to find that there are remarkable discrepancies in the distribution and shade of red circles between the cocrystal and parent drug BFZ, illustrating that there are different intermolecular interactions in their structures, in terms of both types and strengths. And beyond that, the 2D fingerprint maps also offer reliable support for the foregoing viewpoint, since they summarize the proportional contributions of various intermolecular interactions from a quantitative perspective, which more straightforwardly compares and analyzes the intermolecular interactions among the different systems.…”

“…By utilizing density functional theory (DFT), the molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) calculations were accomplished by applying Gaussian 09 software at the B3LYP/6-311G(d,p) basis set. 35,36 Therein, MEP maps were rendered on an 0.004 Bohr Å −3 electron density isosurface via Multiwfn 3.6 software. 37 Additionally, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were displayed using the VMD program.…”

“…The solubility of the original drug BFZ, the cocrystal BFZ–TPA and the physical mixture (PM) of BFZ and TPA was tested using the excess powder dissolution method. 36 Since BFZ had a very poor aqueous solubility of 0.7 μg mL −1 and cannot be fully dissolved in conventional dissolution media, an ethanol–water (1 : 9, v/v) binary solvent system was chosen to enhance dissolution based on a previous literature method. 39 Before excess amounts of samples were added into the corresponding buffer solutions of pH 4.0 and 6.8, they were respectively ground and sifted through 100 mesh sieves to obtain a uniformly sized sample and minimize the size effect on solubility behaviors.…”

Trimorphic forms of 5-fluorocytosine–gentisic acid with enhanced hydration stability

“…18–20 Two polymorphs, hydrates, and cocrystals/salts of 5FC were reported in the literature with various GRAS and drug coformers. 21–30 However, polymorphic cocrystals of 5FC are not reported so far. The chosen coformer gentisic acid (GEA) is a phenolic acid derivative that has some useful effects on health such as anti-inflammatory, anti-genotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities.…”