Enrichment of chlorthalidone enantiomers by an aqueous bulk liquid membrane containing β-cyclodextrin

A single (one membrane and one strip phase) and a multiple (three membranes and three strip phases) bulk liquid membrane (BLM) containing β-cyclodextrin (CD) as chiral mobile carrier was used for the chiral enrichment of racemic chlorthalidone (CT). Initial solubility and partitioning data of CT in ethylacetate (EtOAc) (feed and strip phase) and in water (membrane phase) gave a distribution coefficient (Kd = [CT]aq/[CT]EtOAc) of 0.04 and a ΔG for complexation of +7.8 kJ mol−1. The influence of both pH and carrier concentration on BLM enrichment was evaluated. In spite of the small Kd and positive ΔG, chiral enrichment was feasible and the highest selectivity (α = 1.41) was obtained with the multiple BLM at low pH (pH = 5) and low relative carrier concentration (CD : CT ratio = 1 : 4). The low pH reduced solubility and thus passive transport of CT in the membrane phase. Both the improvement of selectivity at lower [CD] and the fact that the highest selectivity under all conditions was during the initial stages of the membrane process, illustrated that complexation was kinetically driven.