| A Supercritical Chromatography System is developed for separation of chiral isomers. The systems studied include ibuprofen as well as of flurbiprofen, a non-Steroidal Anti- Inflammatory Drug (NSAID). S-isomer is used for various pain treatments such as Rheumatoid Arthritis and Osteoarthritis while R-isomer is used in cancer research. The column utilized for this method was a Pirkle brush-type Whelk-O 1 analytical column packed with 10 m m particles. Carbon dioxide is used as a mobile phase with several different organics employed as a modifier. The effect of pressure, temperature, flow rate and modifier content on the separation factor, peak resolution and retention time is analyzed. Elution chromatography is used to abstract isotherm information for scale up and synthesis of operating policies for fractionation through simulated moving bed.
Supercritical fluid chromatography (SFC) is most often used with carbon dioxide as a mobile phase and an organic modifier such as some type of organic alcohol. It has some significant advantages over standard HPLC methods such as less pressure drop across the columns, faster column equilibration, faster method development, higher efficiency separations and significantly less generation of hazardous waste. Some of the main advantages for preparatory chromatography include solvent waste reduction, facilitated product recovery, lower solvent cost and the possibility for solvent recycling.
Two chiral drug systems were studied in this body of work. The first is Ibuprofen, a nonsterodial anti-inflammatory drug which as of late is being studied for its chiralrelated properties. There are several reasons to separate the two isomers (R and S). The first is that the S-isomer works more than twice as fast as the racemic mixture. This allows for therapeutic applications that require more speed than would be impossible with the mixture. The other reason is that the effective dosage of the drug is decreased. The second system is flurbiprofen, a non-Steroidal Anti-Inflammatory Drug (NSAID). Sisomer is used for various pain treatments such as Rheumatoid Arthritis and Osteoarthritis while R-isomer is used in cancer research.
Chromatographic techniques and technologies are currently in wide spread use for analytical and preparative purposes in industry. In many cases, the only method to obtain pure components is chromatography; this is especially true for isomers and enantiomers. Chiral separations are relatively new capabilities that are based on the elution chromatography model, but special stationary phases have to be utilized to achieve separation. The most often produced stationary phases are made of polysaccharides or proteins, but these are much more delicate than the standard C18 and C8 columns and tend to have a much shorter operational life expectancy. The reason for this delicate nature is that chiral stationary phases are not covalently bonded to the silica support like the C18 and C8 columns.
Several different modifiers were used to find what organic or combination of organics produced the best results. The modifiers that were used in the experiments were around 10 volume percent in carbon dioxide. The specific organics used as modifiers were isopropanol, ethanol, methanol, ethyl acetate, acetone, and combinations of equal amounts by volume of isopropanol and ethanol, isopropanol and methanol, ethanol and methanol, ethyl acetate and isopropanol, as well as a 9.4% and 0.6% combination of hexane and isopropanol. |