DIFFERENTIAL SCANNING CALORIMETRIC STUDY ON THE KRAFFT PHENOMENON OF LOCAL-ANESTHETICS

The Krafft phenomenon of six local anesthetics--tetracaine hydrochlori de (TC . HCl) and hydrobromide (TC . HBr); dibucaine hydrochloride (DC . HCl), hydrobromide (DC . HBr), and hydroiodide (DC . HI); and bupiv acaine hydrochloride (BC . HCl)--was investigated by differential scan ning calorimetry (DSC) of the aqueous anesthetic solutions. The aqueou s solutions of TC . HCl, BC . HCl, TC . HBr, and DC . HI showed the Kr afft phenomenon, while those of DC . HCl and DC . HBr did not. The ent halpy change of phase transition from the coagel phase (or the so-call ed hydrated crystal) to the micellar solution (Delta H-t) for the anes thetics was determined directly from the DSC thermograms of local anes thetic solutions at different concentrations, The Krafft temperature a nd the critical micelle concentration (CMC) for these anesthetics were determined from the solubility vs temperature curves. The Krafft temp eratures of these anesthetics were greatly dependent on the chemical s tructures of hydrophobic groups in the molecules and on the negative h alide counterions. It was also found that the local anesthetics have l arger CMC values and smaller Delta H-t ones than straight-chain surfac tants such as alkyltrimethyammonium bromide. This is attributable to t he weak hydrophobicity of local anesthetic molecules compared with the surfactant molecules. The difference in the solution behavior between TC . HCl and BC . HCl in water was considered using the enthalpy chan ge of the transition among the three states of anesthetic assembly: co agel phase,single dispersion,and micellar solution. (C) 1996 Academic Press, Inc.