The interaction of charged and uncharged drugs with neutral (HP-β-CD) and anionically charged (SBE7-β-CD) β-cyclodextrins

The objective of this work was to determine the role that charge might play in the interaction of charged and uncharged drugs with neutral (2-hydroxypropyl-beta-cyclodextrin, HP-beta-CD) and anionically charged (SBE7-beta-CD) modified beta-cyclodextrins. SBE7-beta-CD is a sulfobutyl ether, sodium salt, derivative variably substituted on the 2-, 3- and the 6-positions of beta-cyclodextrin. The number seven refers to the average degree of substitution. The binding of the acidic drugs, indomethacin, naproxen and warfarin and the basic drugs, papaverine, thiabendazole, miconazole and cinnarizine with the two cyclodextrins was determined at 25 degrees C as a function of pH and cyclodextrin concentration by the phase-solubility method. Except for miconazole and cinnarizine (Ap-type diagrams), all other materials studied displayed AL-type diagrams. By comparing the binding constants of both the charged and uncharged forms of the same drugs to both HP-beta-CD and SBE7-beta-CD, the following conclusions could be drawn. The binding constants for the neutral forms of the drugs were always greater with SBE7-beta-CD than with HP-beta-CD. For the anionic agents, the binding constants between SBE7-beta-CD and HP-beta-CD were similar while the binding constants for the cationic agents with SBE7-beta-CD were superior to those of HP-beta-CD, especially when compared with the neutral form of the same drug. A clear charge effect on complexation, attraction in the case of cationic drugs and perhaps inhibition in the case of anionic drugs, was seen with the SBE7-beta-CD.