P Boudeville, J L Burgot
Index: J. Pharm. Sci. 84(9) , 1083-9, (1995)
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A new methodology of pH-metric data treatment was developed to extract the stoichiometry and the thermodynamic association constants of guest-cyclodextrin inclusion complexes in dilute aqueous solution when the guest is a participant in an acid-base equilibrium. pH-metric titration curves in the presence of cyclodextrin (CD) were treated by a curve-fitting technique according to a nonlinear least-squares regression. Equations corresponding to the different kinds of acid-base pairs (AH/A-, BH+/B) and stoichiometries (1:1 and 1:2) were established. The methodology was validated by studying the 5-phenylbarbituric acid complexation with beta-CD and the 4-cyanobenzoic acid complexation with alpha-CD. Then it was applied to chlorpromazine. Both the acid form (constant K1 = 3260) and the base form (constant G1 = 13,100) gave complexes with beta-CD according to 1:1 stoichiometry.
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