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

Abstract

Poor solubility of new antifungal of 1,2,4-triazole class (S-119)—a structural analogue of fluconazole in aqueous media was estimated. The solubility improvement using different excipients: biopolymers (PEGs, PVP), surfactants (Brij S20, pluronic F-127) and cyclodextrins (α-CD, β-CD, 2-HP-β-CD, 6-O-Maltosyl-β-CD) was assessed in buffer solutions pH 2.0 and pH 7.4. Additionally, 2-HP-β-CD and 6-O-Maltosyl-β-CD were proposed as promising solubilizers for S-119. According to the solubilization capacity and micelle/water partition coefficients in buffer pH 7.4 pluronic F-127 was shown to improve S-119 solubility better than Brij S20. Among biopolymers, the greatest increase in solubility was shown in PVP solutions (pH 7.4) at concentrations above 4 w/v%. Complex analysis of the driving forces of solubilization, micellization and complexation processes matched the solubility results and suggested pluronic F-127 and 6-O-Maltosyl-β-CD as the most effective solubilizing agents for S-119. The comparison of S-119 diffusion through the cellulose membrane and lipophilic PermeaPad barrier revealed a considerable effect of the lipid layer on the decrease in the permeability coefficient. According to the PermeaPad, S-119 was classified as a highly permeated substance. The addition of 1.5 w/v% CDs in donor solution moves it to low-medium permeability class.

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis

“…albicans. Furthermore, increasing the solubility of FNL would contribute toward the therapeutic performance, in this case the antimicrobial activity of FNL …”

Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine

“…The apparent permeability coefficients were measured at 37 °C with the help of a vertical-type Franz diffusion cell (PermeGear, Inc., Hellertown, PA, USA). The experimental setup was the same as it was described in our previous study [ 40 ], where the excess amount of the investigated substance was placed in glass cups with ground-in lids. The required volume of buffer pH 6.8 without and with a predetermined concentration of the excipient (F127 or SBE-β-CD in the present study) was added, and the suspension was mixed overnight and filtered to obtain a clear solution.…”

Revisiting the Solubility–Permeability Relationship with Hydrophobic Drug Umifenovir in Pluronic Solutions: Impact of pH and Co-Solvent

“…The permeability coefficients of UMF were measured in a Franz diffusion cell of a vertical type (PermeGear, Inc., Hellertown, PA, USA) at 310.15 ± 0.1 K. The experimental setup is fully described and illustrated in our previous study [ 34 ]. All the experiments were carried out with the help of a regenerated cellulose membrane with a molecular weight cut-off (MWCO) of 12–14 kDa (Standard Grade RC Dialysis Membrane, Flat Width 45 mm) pretreated with water for 30 min and dried under air.…”