Interaction of some benzothiadiazine diuretics with beta-cyclodextrin

The interaction of three structurally related benzothiadiazine diuretics, viz., hydroflumethiazide, bendrofluazide and cyclopenthiazide wit beta-cyclodextrin was investigated. The study aimed at enhancing the solubility of these poorly soluble drugs via inclusion complexation with beta-cyclodextrin, Solubility measurements revealed that complexes were formed between each of three drugs and beta-cyclodextrin, The complexes were found to have 1:1 stoichiometric ratios and stability constants of 165.4, 55.7 and 27.9 M-1 for cyclopenthiazide, bendrofluazide and hydroflumethiazide, respectively. UV spectrophotometric analysis of the formed complexes agreed with the solubility results. The variation in the extent of binding between each of the three drugs and beta-cyclodextrin was attributed to their variation in molecular volume, partition coefficient and electrostatic properties of the binding sites.