K. Okimoto et al., THE INTERACTION OF CHARGED AND UNCHARGED DRUGS WITH NEUTRAL (HP-BETA-CD) AND ANIONICALLY CHARGED (SBE7-BETA-CD) BETA-CYCLODEXTRINS, Pharmaceutical research, 13(2), 1996, pp. 256-264
Purpose. The objective of this work was to determine the role that cha
rge might play in the interaction of charged and uncharged drugs with
neutral (2-hydroxypropyl-beta-cyclodextrin, HP-beta-CD) and anionicall
y charged (SBE7-beta-CD) modified beta-cyclodextrins. SBE7-beta-CD is
a sulfobutyl ether, sodium salt, derivative variably substituted on th
e 2-, 3- and the 6-positions of beta-cyclodextrin. The number seven re
fers to the average degree of substitution. Methods. The binding of th
e acidic drugs, indomethacin, naproxen and warfarin and the basic drug
s, papaverine, thiabendazole, miconazole and cinnarizine with the two
cyclodextrins was determined at 25 degrees C as a function of pH and c
yclodextrin concentration by the phase-solubility method. Results. Exc
ept for miconazole and cinnarizine (A(P)-type diagrams), all other mat
erials studied displayed A(L)-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 a
lways 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 compare
d with the neutral form of the same drug. Conclusions. A clear charge
effect on complexation, attraction in the case of cationic drugs and p
erhaps inhibition in the case of anionic drugs, was seen with the SBE7
-beta-CD.