Comparative analysis of solubilization and complexation characteristics for new antifungal compound with cyclodextrins. Impact of cyclodextrins on distribution process

Chiral Recognition R- and RS- of New Antifungal: Complexation/Solubilization/Dissolution Thermodynamics and Permeability Assay

“…In pure buffer solutions it varies from 1.8 × 10 −5 /2.7 × 10 −5 M at pH 7.4 to 6.2 × 10 −4 /5.0 × 10 −4 M at pH 2.0 for R-98/RS-186, respectively. Bearing in mind that the investigated structure is very close to the previously reported [19,26] L-173 (Figure S2) it was interesting to compare the solubility of these substances. Besides this, both L-173 and the investigated compounds include a fragment of fluconazole (FCZ) (the structure is shown together with L-173 in Figure S3), thus making it reasonable to compare this well-studied antifungal with the other.…”

“…It is likely that a blue shift upon the decrease of the acidity of the buffer was due to an increase in the hydrogen bonding capacity of the solvent [23]. As opposed, no shifting was observed to the structurally analogous compound L-173 (its structure is given in Figure S3 Supporting Information) investigated in our previous study [19]. It is well known that the UV spectrum is sensitive to the dielectric properties of the medium [24].…”

“…In our previous study, on the example of a novel potential antifungal compound [19], we applied an approach aimed at the understanding of the driving forces of the molecule transition from pure buffers to the CD solutions upon the simultaneous solubilization and complex formation. Since the magnitudes of the standard free energy and entropy changes depend on the standard state, the mole fraction unitary units which provide better chemical interpretation were used for an accurate comparative analysis of the solubililization and complexation processes in the CD solution.…”

“…The application of the approach described above (Issue 1) to the enantiomer/racemate discrimination provides a more detailed insight into the enantiomeric differentiation in respect to the two considered processes: complexation and solubilization. Moreover, similar to Yonemochi et al [21], the free energy difference of the complexation, solubilization and inherent dissolution of the racemic compound and its enantiomer can be calculated using Equations ( 17)- (19), respectively:…”

Modulation of Distribution and Diffusion through the Lipophilic Membrane with Cyclodextrins Exemplified by a Model Pyridinecarboxamide Derivative

“…Many chemically modified β-cyclodextrins, such as hydroxypropyl- or methyl-substituted ones, are successfully used in pharmaceutical products [ 19 ]. Cyclodextrins impact the properties of drugs (solubility, distribution, permeability) in different modes, which was demonstrated in the literature [ 20 , 21 , 22 , 23 ], including some studies carried out by our scientific team [ 11 , 24 , 25 ]. This comes from the fact that among the many factors which can influence the character of drug–cyclodextrin interaction, the most important one is the nature of the cyclodextrin used [ 26 , 27 ].…”