Enantioselective Release Behavior of Ketoprofen Enantiomers from Alginate-metal Complexes, Monitored by Chiral HPLC

Alginate-metal complexes were prepared with divalent (Ca, Ba, Zn) and trivalent metals (Fe, Al) via congealing method in form of beads. Alginate mixed metals (Ca and Fe) complexes were also prepared by simultaneous and consecutive congealing. The studied beads were blank beads and racemic ketoprofen (KTP) loaded beads. Metal content was determined by atomic absorption spectroscopy and was 1.8% to 30.4%. The IR spectra showed interactions between ketoprofen carboxylic OH and alginate hydroxyl OH, thus chiral interaction is suggested. Chiral HPLC was used to monitor enantioselective release (ESR) of racemic ketoprofen enantiomers in a phosphate buffer solution (PBS) at pH = 7.4. ESR is expressed as the relative chromatographic area of R-enantiomer to S-enantiomer (R/S ratio). For divalent metal complexes, over the first 50 min of release, R/S was < 1; with starting value of 0.53 in case of calcium, indicating important ESR, but less important in case of barium. However, in case of zinc, R/S was >1 with starting value of 1.1, indicating weak ESR. No significant results of ESR were obtained for trivalent metal complexes, where R/S is almost 1 in case of iron and aluminum. For alginate beads, which simultaneously congealed with (Ca and Fe), R/S was >1. Nevertheless, consecutively congealed alginate gave opposite ESR behavior; R/S was <1 for Ca then Fe congealed alginate, while R/S was >1 for Fe then Ca congealed alginate.