THE EFFECT OF WATER-SOLUBLE POLYMERS ON DRUG-CYCLODEXTRIN COMPLEXATION

In aqueous solutions water-soluble polymers were shown to increase the solubilising effect of cyclodextrins on drugs. For example, the solubilising effect of 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) with molar substitution of 0.6 was improved by 6-57% (on average 27%) when 0.25% (w/v) carboxymethylcellulose was present in the solution and 12-129% (on average 49%) when 0.25% (w/v) polyvinylpyrrolidone (PVP) was present. Similar results were obtained with other cyclodextrins and other polymers. For PVP and 10% (w/v) HP beta CD the PVP concentration for maximum solubilisation appeared to be between 0.05 to 0.25% (w/v). At this low concentration PVP had insignificant effect on the viscosity of the aqueous HP beta CD solution. The polymers increased the stability constants of the drug-cyclodextrin complexes. Addition of PVP to the aqueous complexation medium resulted in an increased negative enthalpy change, together with an increased negative entropy change.