Abstract
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
Highlights
With the constant growth of the number of medicinal products on the market, the threat of polypharmacy is growing
As it can be seen from the Nyquist diagrams (Fig. 3), the addition of iron (III) chloride to doxycycline hyclate lead to a change in electroimpedance spectral characteristics either in shape (the diameter of the impedance semicircle decreased compared to the corresponding diagrams for pure doxycycline hyclate solution (Fig. 2, b), or the clear appearance of the Warburg im
Electrochemical impedance spectroscopy (EIS) analysis of Nyquist curves of doxycycline hyclate and iron (III) chloride aqueous 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, which can be considered a qualitative sign of complexation at this point
Summary
With the constant growth of the number of medicinal products on the market, the threat of polypharmacy is growing. By building the appropriate electrical model based on the results of total impedance measurements and calculating its elements, it is possible to assess the peculiarities of chemical processes and draw conclusions about the complexation between the studied substances and metal salts. During our research, both approaches were used – qualitative estimation by Nyquist curves and modeling by values of an electric circuit, as well as quantitative estimation of its elements and determination by their dynamics of electrochemical processes occurring in the studied solutions. ZIm= (ZRe) were determined [15]
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