Study On The Thermodynamic Behavior Of Cephalosporins In Simulated Biological Solutions

Cephalosporins are semi-synthetic broad-spectrum antibiotics which are modified by cephalosporin C. Currently, more and more researches and developments are focused on cephalosporins because of its high efficacy, broad spectrum antimicrobial and antibacterial activity. However some byeffects and anaphylactic reaction occurred occasionally due to domestic cephalosporins poor quality control. Suported by Natural Science Foundation of Henan Education Department (2008A530004), the solubilities and the thermodynamics for dissolving process, refractive indices, electrical conductivity, the volume properties as density and transferring properties as viscositiy of cephalosporins in simulated biological solutions are studied systematically in this paper. The results will have a great significance in scientific theory and engineering applications.Using the laser monitoring observation technique, the solubilities of three cephalosporins including cefepime hydrochloride, cefodizime sodium and cefpirome sulfate in water, water+methanol, water+ethanol, water+1-propanol and water+ 2-propanol were measured in the temperature range from 278.15 K to 308.15 K. The experimental data were correlated with a simple model of molecular thermodynamics for solubilities of solid in liquid and the model parameters were obtained completely. The dissolution enthalpies?solH and dissolution entropies?solS of the three cephalosporins in water and water+alcohol were estimated.?solH> 0 reveals that the interactions between the cephalosporins and solvent molecules are weaker than those between the solvent molecules. The dissolved process is endothermic and the break of association bond is principal. The positive?solH and?solS reveal that the dissolution process of the three cephalosporins in the studied systems were entropy-driven processes.?solS> 0 shows that when cephalosporins dissolved into solvents, the array of solvents molecular was disturbed, the degree of order decrease, randomness increases and entropy increases.The densities, viscosities and refractive indices of cefepime hydrochloride (or cefodizime sodium, ceftriaxone sodium and cefotaxime sodium)+water (or 0.9 mass % normal saline) binary and ternary solutions were measured at different concentrations in the tempreture range from 278.15K to 313.15 K.The Vogel-Tamman-Fulcher Equation was used to correlate the densities variation with temperatures and concentrations successfully by least square method. Apparent molar volumes, standard partial molar volumes, standard partial molar volume expansivities of cephalosporins in binary or ternary solutions were calculated based on experimental densities. Changes in relative viscosity and viscosity B-coefficient of the four cephalosporins were calculated from viscosity experimental data. The variation rules of volume properties and viscosity properties were discussed from the aspect of molecular interactions. Solute-solvent interaction, solute-solute interaction and structure-breaking effect of the four cephalosporins have been discussed using the Helper rule and Jones-Dole equation.A molecular thermodynamic model of refractive indices for multicomponent solutions was proposed, based on the molecular model for solution structure and equation for the excess enthalpy of a binary solution. The model parameters were determined by nonlinear least square method from the experimental measurements. Compared the calculated data by model with the experimental data, the total standard deviation of the 536 data points in 81 systems is 1.095×104.The conductivity of cefepime hydrochloride (cefotaxime sodium or ceftriaxone sodium)+saline water ternary solutions were determined in the tempreture range from 278.15K to 313.15 K and the molar conductivity was calculated. The molar conductivity depending on the molality of solutions were correlated with the modified Kohlrausch equation, and the limiting molar conductivities were obtained at different temperatures for the three systems. The limiting molar conductivities were linearly correlated with temperatures. The relationship between the molar conductivity and temperature submits to Arrhenius Equation. In view of the above, the activation energy for conductivity and the limiting activation energy for conductivity can be obtained.The results not only provide the academic datas for the behavior of thermodynamics of cephalosporins in simulated biological solutions such as water+ alcohol and normal saline, but also provide foundations for the improvement of production technology, the studies of pharmacodynamics and relevant molecular thermodynamics as well. The research will be sure to promote the development of relevant subjects.