Thermodynamics of antibiotics: natural cyclodextrin inclusion complex formation and covering of nano-metric calcite with these substances

Abstract

Isothermal titration calorimetry (ITC) has been used to characterize inclusion complex formation of natural (α-, β-, γ-)cyclodextrins with antibiotics (ampicillin—sodium, penicillin G—sodium, streptomycin sulfate) in aqueous solutions. ITC measurements were taken at 298.15 K on Isothermal Titration Calorimeter Nano ITC. The experimental data were analyzed on the basis of the independent site model. Based on the experimental values of equilibrium constant (K) and enthalpy of complex formation (ΔH), the Gibbs energy of complex formation (ΔG) and the entropy of complex formation (ΔS) have been calculated. The analysis of the obtained inclusion complexes show that independently of the kind of cyclodextrin and antibiotics the obtained equilibrium constants are almost the same, but it is a difference between the changes in enthalpies of complex formation for the investigated systems. The stoichiometry of complexes formed both by ampicillin—sodium and by penicillin G—sodium with all the natural cyclodextrins is the same and equal to 1:1 and the complex formation is entropy driven. Three antibiotics (ampicillin—sodium, penicillin G—sodium and streptomycin sulfate) have been used further for covering of the monodisperse calcium carbonate nanoparticles obtained in the reactor (three-phase reaction) with rotating disks. Three series of experiments have been performed. First was connected with adsorption of the antibiotics on the surface on nano-calcite and two others with intercalation of the drugs into nano-metric CaCO3 structure (aggregates). An intercalation has been performed in two ways: one where the antibiotic was added to the reactor chamber at the beginning of the precipitation reaction and second where it was added just after the end of the reaction. Both pure CaCO3 nanoparticle and antibiotic-coated CaCO3 powders were deeply analyzed by the use of the thermogravimetric and the differential scanning calorimetry method. The performed investigations showed that all the antibiotics used can be both adsorbed and intercalated into the nano-metric CaCO3 obtained in the reactor with rotating disks. The different adsorption obtained by different antibiotics was caused by the different interaction between them and nano-calcite, caused by their different structure. The experimental data have allowed also for distinction between the antibiotics molecules present on calcite surface (adsorption) or antibiotics molecules intercalated into the nano-calcite structure. The conducted research shows that both approaches, i.e., formation of inclusion complexes with natural cyclodextrins and covering (adsorption and intercalation) of nano-metric CaCO3, can be successfully implemented for their pharmaceutical applications.