Physicochemical profile of new antifungal compound: pH-dependent solubility, distribution, permeability and ionization assay

New Antifungal Compound: Impact of Cosolvency, Micellization and Complexation on Solubility and Permeability Processes

“…As it was shown in our previous study [32] by PXRD experiment, S-119 is a solid crystalline substance. It has poor solubility in aqueous media (4.45•10 −3 M and 4.01•10 −5 M in buffers pH 2.0 and pH 7.4, respectively, at 25 • C), which would be a reason for its inadequate transport properties and bioavailability.…”

“…As an example, the plots of UV spectra for the solutions in buffer pH 7.4 are introduced in Figure S1 (Supplementary Materials). As previously shown [32], the solubility of the substance is affected by the pH of aqueous medium. Due to this fact, the experiments were carried out in two pHs in order to reveal the simultaneously impact of the pH and excipient on the solubility.…”

“…Besides this, the increased dissolution rate of fluconazole in solid dispersions with β-cyclodextrin, PEG-6000 and PVP K30 was demonstrated [31]. Taking into account the results of our previous study [32] where a poor solubility of S-119 in aqueous solutions was estimated (4.45 × 10 −3 mol•L −1 at pH 2.0 and 4.01 × 10 −5 mol•L −1 at pH 7.4) and data from the literature review it seemed reasonable to check the possibility of S-119 solubility improvement via cyclodextrins and polymers.…”

“…) was synthesized at the Gause Institute of New Antibiotics (Moscow, Russia). Synthetic procedure applied to the synthesis of S-119 was reported in the previous study [32].…”

“…Undoubtedly, the lipophilicity of the compounds plays a crucial role in the interactions with the hydrophobic CD cavity. According to logD oct = 0.5 [41], FCZ belongs to the substances of moderate lipophilicity, whereas for S-119 logD oct = 1.43 [32]. The K S values for the cationic species of FCZ in acidic solution were shown to be lower (10.7 and 13.5 M −1 ), similarly to S-119, according to a poor affinity of the charged particles to the hydrophobic cavity of CD [42].…”