CRITICAL MICELLAR CONCENTRATION SHIFTING AS A SIMPLE TOOL FOR EVALUATING CYCLODEXTRIN ENHANCER INTERACTIONS/

It has previously been found that the undesirable side effects of enha ncers may be reduced, virtually without affecting their promoting abso rption actions, when they are used in combination with a cyclodextrin. Many enhancers are amphiphilic moieties able to form micelles in solu tion. The enhancing effect is ascribed to the free molecules in soluti on. Their toxic effects seem to be linked to the solubilization of cel l membrane components (such as phospholipids or cholesterol), due to m icelles formed by the enhancers. A study on the influences of cyclodex trins on critical micellar concentration (cmc) shifting has been carri ed out by surface tension measurements. The formation of a complex in solution between the cyclodextrin and the enhancer shifts cmc to highe r values, and changes the ratio between free and micellized molecules of the enhancer, thus minimizing its toxic effects. Laureth-9, quatern ary ammonium salts and cholic acid derivatives were considered as enha ncers. Changes in buffering salts and tonicity of the measuring medium were also taken into consideration as formulative variables.