USE OF A NONLINEAR LEAST-SQUARES MODEL FOR THE KINETIC DETERMINATION OF THE STABILITY CONSTANT OF CYCLODEXTRIN INCLUSION COMPLEXES

The nonlinear least-squares model for the calculation of the stability constants (K-st) of drug:cyclodextrin complexes was used in kinetic s tudies. Complexation of riboflavin (R) with hydroxypropyl-beta-cyclode xtrin (HP:beta-CD) was monitored kinetically by measuring the rate of photodegradation of R exposed to ultraviolet light in the presence of increasing concentrations of HP:beta-CD. Formation of inclusion comple x was confirmed in aqueous solution by proton nuclear magnetic resonan ce spectroscopy (H-1-NMR). The experimental K-st value (3321 M(-1)), d erived from the kinetic studies. appeared to fit well to a 1:1 drug:cy clodextrin molar ratio according to the nonlinear mathematical model. The model is particularly suitable for the study of cyclodextrin as a stabilizing system for compounds that are sensitive to light, oxygen, temperature or the media which contain them. Copyright (C) 1996 Elsevi er Science B.V.