Effect of antidiabetic drug metformin hydrochloride on micellization behavior of cetylpyridinium bromide in aqueous solution

Abstract

Herein, the interaction of an antidiabetic drug, metformin hydrochloride (MHCl), and a cationic surfactant, cetylpyridinium bromide (CPB) is investigated in an aqueous medium. The critical micellar concentration (CMC) of CPB is estimated through conductivity experiments and found to be reduced on adding MHCl and further decreased in the presence of NaCl. The reduced CMC is attributed to the solubilization of MHCl by CPB through micellization and the micellization is found to be thermodynamically spontaneous that experiences an augmentation in the presence of NaCl. This is identified from the negative value of standard free energy ($\Delta$G⁰_m). The higher negative value of $\Delta$G⁰_m (-55.41 kJ mol⁻¹) for CPB + MHCl + NaCl than CPB (-37.89 kJ mol⁻¹) and CPB + MHCl (-34.08 kJ mol⁻¹) is suggestive of the above phenomenon. The positive values of $\Delta$S⁰_m in all three cases confirm that the micellization is entropy driven. The binding of MHCl on CPB is quantified by estimating binding constant using the Benesi-Hildebrand (B-H) plot through UV-visible spectral methods. The binding constant values were calculated to be 2.70 M⁻¹ for CPB + MHCl + NaCl compared to 1.258 M⁻¹ for CPB + MHCl predicting a favoring of micellization in the presence of NaCl which is higher than that in the presence of co-solvents. The molecular interaction of MHCl and CPB is justified using FT-IR and NMR techniques. The surface properties of drug surfactant interactions are assessed using SEM techniques. The point of interaction between the drug and surfactant is visualized through the molecular docking approach. The results suggest that CPB would be an effective solubilizer for developing MHCl drug formulations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cetylpyridinium bromide
• metformin hydrochloride
• micellization of metformin hydrochloride
• anti-diabetic
• critical micellar concentration

Authors’ contribution

Methodology, Validation, Formal analysis, Investigation, Anjali S., Data curation, Writing—original draft, Vigneshwari R., Writing—review & editing, Visualization. Sivakumar K., Conceptualization, writing—review and editing, Supervision, and project administration. Formal analysis, Writing—original draft, Dr. Sasmita Dash.

Disclosure statement

The authors state that they have no conflict of interest in this article.

Additional information

Funding

Funding sources are not available for this work.