A physico-chemical study on the interaction between papaverine and natural and modified beta-cyclodextrins

The interaction of the alkaloid drug papaverine (PAP) with different cyclodextrins (CyDs) was investigated. Freeze-drying method was used to prepare solid complexes that were characterized in the solid state using differential scanning calorimetry (DSC) and X-ray diffractometry. Circular dichroism spectroscopy (CD) and 1H-NMR was used in an aqueous solution to obtain information about the inclusion mode of PAP into the cavity of CyDs. β-cyclodextrin (β-CyD) and dimethyl-β-cyclodextrin (DM-β-CyD) are able to include the drug but in all cases the stability constant values are very small, indicating a weak host-guest interaction. No exact information exists about the interaction of PAP with the internal cavity of hydroxypropyl-β-cyclodextrin (HP-β-CyD). Solubility studies in the presence of all CyDs were performed using Higuchi and Connors methods at 37°C and pH 7.4. The influence of complexation on the diffusion rate of PAP through artificial membranes was evaluated using dialysis bags. Little influence was observed in the presence of all macrocycles.