HPLC and solubility study of the interaction between pindolol and cyclodextrins

The complexation with β-cyclodextrin (β-CD) has been investigated using reversed-phase liquid chromatography. The compounds tested have been pindolol and, for comparison purposes, indole and 4-methoxyindole. The retention behaviour has been analysed on a Kromasil 100 C18 column and the mobile phase used was methanol-pH 6 phosphate buffer (15/85 v/v) in which β-CD was incorporated as a mobile phase additive. The decrease in the retention times with increasing concentrations of β-CD enables the determination of the apparent stability constants of the complexes. In addition, the low solubility of pindolol, a weak base, in pH 12 aqueous solution has been improved by complexation with different cyclodextrins. The solubility enhancements with 1.4 × 10−2 M β-, hydroxypropyl-β, and γ-CD have been 1.9, 1.8 and 1.4-fold, respectively, with 2.4 × 10−2 M methyl-β-CD it was 2.8-fold whilst no effect was observed with α-CD. The stability constants of the complexes at pH 12 have been determined from the solubility isotherms.