Complex of Calcium Receptor Blocker Nifedipine with Glycyrrhizic Acid

Physicochemical methods were used to explore the regularities of complexing between the calcium channel blocker nifedipine (NF) and pharmaceutically acceptable complex-forming glycyrrhizic acid (GA) in view of the discovered influence of GA on the therapeutic activity of NF. 1H NMR (including relaxation measurements) and UV−vis spectra have produced illustrative evidence that NF forms stable complexes with GA within a wide concentration range, from 0.05 to 5 mM. At low GA concentrations, below 0.5 mM, NF forms an inclusion complex where each NF molecule is bound by two molecules of GA. Computer simulations of the NMR experimental data have shown that, in aqueous solution, the stability constant of this complex, K, is about 105 M-1. At higher concentrations, GA forms large micelle-like aggregates which increase the water solubility of NF. Quenching of chemically induced dynamic nuclear polarization effects in the photoinduced interaction of the NF−GA complex with tyrosine suggests that complex formation with GA completely blocks the single electron-transfer step between NF and the amino acid. This, arguably, could explain the increased therapeutic activity of GA complexes, since GA might protect the drug molecule from the reaction with amino acid residues of the receptor binding site.