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

• Published in: European journal of pharmaceutical sciences Vol. 154; p. 105531
• Main Authors: Volkova, Tatyana V., Perlovich, German L.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.11.2020
• Subjects: Antifungal compound; Distribution coefficient; Solubility-distribution interplay; Stability constant; Antifungal compound; Stability constant; Distribution coefficient; Solubility-distribution interplay
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2020.105531

•Solubility of new antifungal compound in three cyclodextrins at pH 2.0 and pH 7.4 was studied by phase-solubility method in temperature range 298-313.15 K.•Comparative analysis of complexation and solubilization processes using thermodynamic approach was carried out.•Impact of cyclodextrins on the distribution of the compound in octanol/water and hexane/water systems was assayed at pH 2.0 and pH 7.4 at 298 K.•Optimal cyclodextrin concentrations were proposed based on the solubility and distribution studies. From a pharmaceutical standpoint, cyclodextrin-based products have deservedly gained substantial market share due to their ability to improve undesirable physicochemical properties of drugs. In this study the solubility of a potenial antifungal compound (L-173) has been improved essentially by addition of β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) in aqueous solutions (pH 2.0 and pH 7.4) at 298.15–313.15 K. The phase solubility diagrams were constructed. The stoichiometric ratio of the complexes was determined as 1:1. The stability constants of L-173 with all three CDs in acidic medium belong to the range optimal for the improvement of the bioavailability of hydrophobic drugs. DM-β-CD was assigned as the best solubilizer for L-173. The driving forces of the solubilization and complexation process were revealed by evaluating the thermodynamic parameters. The distribution behavior of L-173 in the 1-octanol/buffer and 1-hexane buffer systems at pH 2.0 and pH 7.4 in the presence of different CDs concentrations was studied. The reduction of the distribution coefficients with the increasing of CD concentration was detected due to complex formation. Based on the analysis of the solubility-distribution relationship, the L-173 partitioning between the biological tissues and penetration through the biological membranes in case when cyclodextrins are used as solubilizers was evaluated, and the optimal CD concentrations were proposed. [Display omitted]