.2 - Aryl Propionic Acid Class Of Drugs Enantiomers Chromatography Split

Chromatography is now one of the most important methods for the separation of drugs' enantiomers. Supercritical (or Subcritical) Fluid Chromatography (SFC) has the properties of high performance and speed, and conditions being prone to switch. It has become a supplement for High Performance Liquid Chromatography (HPLC) in the field of chiral separation, and has a bright application future. The recent progress in all kinds of techniques for obtaining optical naproxen and ibuprofen was reviewed, and the separation of naproxen and ibuprofen enantiomers by HPLC and SFC was studied comprehensively in the thesis.It was studied that the effect of the composition of the mobile phase, pH and temperature on the separation of naproxen and ibuprofen enantiomers by HPLC on the Chiral-AGP column (150X4.0mm I.D.). In the range of temperature 274 to 313 K, the R-enantiomer is eluted firstly, and the capacity factor, selectivity and resolution of enantiomers decrease as temperature increases. It was also studied that the effect of temperature on the separation of naproxen and ibuprofen enantiomers by HPLC on Kromasil CHI-TBB (250 X 4.6mm I.D.). In the range of temperature 288 to 328 K, the S-enantiomer is eluted firstly, and the capacity factor and selectivity of enantiomersalso decrease as temperature increases.Solubilities of naproxen and ibuprofen in supercritical carbon dioxide were measured on line with a high-pressure ultraviolet detector. The mole fraction solubility of naproxen is between 10"6to 10"5 in the ranges of temperature (308-328K) and pressure (9-19MPa). And that of ibuprofen is between 10-4to 10-3 in the ranges of temperature (308-333K) and pressure (8-15MPa). It can be seen that an increase in pressure of supercritical carbon dioxide results in an increase in solubility of both naproxen and ibuprofen, and the crossover of solubility isotherms occurs when pressure varies. The response factor of ibuprofen decreases linearly as the density of supercritical carbon dioxide increases, and its equation iskt= 422.1-0.3540pIt was studied that the effect of pressure, temperature and modifier concentration on the separation of naproxen and ibuprofen enantiomers by supercritical (or subcritical) carbon dioxide on the Kromasil CHI-TBT column. In the range of pressure 9.0 to 21.3 MPa and temperature 293 to 323 K are best separating condition of naproxen is temperature 293K, pressure 9.4 MPa, and isopropanol concentration 11:89(w/w), and that of ibuprofen is temperature 293K, pressure 12.0 MPa, and isopropanol concentration 2:98(w/w). Every litre Kromasil CHI-TBB column (250mm height) can consume 231 gram of ibuprofen everyday under the best operating condition.The thermodynamic properties of chiral separation were studied, and the thermodynamic parameter (enthalpy changes) for the transfer of enantiomers from the mobile phase to the stationary phase and differences of enthalpy changes (entropy changes) were calculated. The plots of lnk' and ln alpha versus 1/T yielded straight lines in HPLC, respectively. The plots of ln alpha versus 1/T still yielded straight lines but the linear relationship of lnk' versus 1/T could not be observed in SFC. The enthalpic contribution to the overall enantiomer transfer energy was found generally more important than the entropic contribution in the temperature range examined, and lower temperature was good for chiral separation.