STABILIZATION OF IONIC DRUGS THROUGH COMPLEXATION WITH NONIONIC AND IONIC CYCLODEXTRINS

The effects of negatively charged (i.e. carboxymethyl-beta-cyclodextri n and sulfobutylether-beta-cyclodextrin), positively charged (i.e. tri merhylamoniumpropyl-beta-cyclodextrin) and neutral cyclodextrins (i.e. hydroxypropyl-beta-cyclodextrin, acetyl-beta-cyclodextrin and randoml y methylated beta-cyclodextrin) on the chemical stability of various d rugs were investigated. The degradation rate of each drug in aqueous c yclodextrin solutions was determined and the stability constant (K-c) of the drug-cyclodextrin complex and the degradation rate of the drug within the complex (k(c)) was obtained by non-linear fitting of the da ta. Compared to drug complexes with neutral cyclodextrins, the values of K-c were from 20 to 1600% larger when the drug and cyclodextrin mol ecules carried opposite charges, but from 50 to 80% smaller when the m olecules carried the same type of charge. The values of k(c) were not affected by the charge of the cyclodextrin molecule. NMR studies of ch lorambucil complexes indicated that the structure of the cyclodextrin complex was at least in some cases affected by the charge on the cyclo dextrin molecules. (C) 1998 Elsevier Science B.V. All rights reserved.