THE INTERACTION OF CHARGED AND UNCHARGED DRUGS WITH NEUTRAL (HP-BETA-CD) AND ANIONICALLY CHARGED (SBE7-BETA-CD) BETA-CYCLODEXTRINS

Citation
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
Citations number
24
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
ISSN journal
07248741
Volume
13
Issue
2
Year of publication
1996
Pages
256 - 264
Database
ISI
SICI code
0724-8741(1996)13:2<256:TIOCAU>2.0.ZU;2-R
Abstract
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.