Stabilisation of ionic drugs through complexation with non-ionic and ionic cyclodextrins

Abstract

The effects of negatively charged (i.e. carboxymethyl- β-cyclodextrin and sulfobutylether- β-cyclodextrin), positively charged (i.e. trimethylamoniumpropyl- β-cyclodextrin) and neutral cyclodextrins (i.e. hydroxypropyl- β-cyclodextrin, acetyl- β-cyclodextrin and randomly methylated β-cyclodextrin) on the chemical stability of various drugs were investigated. The degradation rate of each drug in aqueous cyclodextrin 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 data. Compared to drug complexes with neutral cyclodextrins, the values of K c were from 20 to 1600% larger when the drug and cyclodextrin molecules carried opposite charges, but from 50 to 80% smaller when the molecules carried the same type of charge. The values of k c were not affected by the charge of the cyclodextrin molecule. NMR studies of chlorambucil complexes indicated that the structure of the cyclodextrin complex was at least in some cases affected by the charge on the cyclodextrin molecules.