Development of the method for estimating complex formation using the electrochemical impedance spectroscopy on the example of the doxycycline and iron (III) interaction

The aim. To develop an EIS method for study the interaction between medicinal products and metal salts on the example of the Doxycycline and iron (III) interaction. Materials and methods. Measurements of the total impedance of the studied solutions have been performed using a vector circuit analyzer ZNB40 (Rohde & Schwarz, Germany). The calculations of electrical models were performed using the software package EC-Lab V10.40. Measurement cell was made of Teflon, 1 ml of volume, had 2 parallel nickel plated steel electrodes with diameter 6 mm, distance between electrodes is 9 mm. Basic electrical elements of model circuit were calculated according to type of electrochemical process that were described by Nyquist plot (RW, Rct, RS, Cd, CS etc.). Solutions were prepared immediately before the measurement. Measurements were performed at a temperature of 296±3 K. 6 control solutions of doxycycline and 6 control solutions of iron (III) chloride were prepared and measured. 11 study solutions at a molar ratio 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1 were prepared and measured. Concentration of the solutions was X∙10-3 mol/L respectively. Results. EIS analysis of Nyquist curves of study solutions in the range of molar ratios 1: 6, 1: 5, 1: 4, 1: 3, 1: 2, 1: 1, 2: 1, 3: 1, 4: 1, 5: 1, 6: 1 showed a change in the dynamics of electrical resistance at a ratio of 1:1. In the aqueous solution at T = 296±3 K the constant formation of the solution of doxycycline hyclate and iron (III) chloride is 2.9. This value of the complexation constant indicates that doxycycline hyclate forms a stable metal-ligand complex with iron (III) ions. Conclusions. EIS method can be applied to study the interaction of medicinal products. Model of this study was created on the example of doxycycline hyclate and iron (III) chloride. Metal-ion complexation of these two molecules was once again confirmed by using the EIS method

A Way to Increase the Bioaccesibility and Photostability of Roflumilast, a COPD Treatment, by Cyclodextrin Monomers

Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with β-CD had the highest K11 value (646 ± 34 M−1), although this value decreased with increasing temperature. Similarly, K11 decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug’s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated.

Remediation of 153Gd-Contaminated Sand by Fulvic and Humic Materials Extracted From Fallen Cherry Leaves

The remediation of sand contaminated with 153Gd has been investigated using natural organic substances extracted from fallen cherry leaves instead of artificial reagents. The initial fulvic and humic acid isolated from organic substances through acidic and basic treatments have a concentration of total organic carbon of 4500 mgC/L and 3340 mgC/L, and the capacities of their functional groups are 7.23 meq/gC and 2.76 meq/gC, respectively. The remediation capacity of both fulvic and humic acid is effective in the weakly acidic region. Remediation with a natural organic substance requires a much higher carbon concentration than EDTA owing to its weak complexation with metal ions. In comparison with the EDTA complexation constant, the experimental complexation constant (log β) of gadolinium with a natural organic substance at pH 5.5 was determined to be 10 at most.