The influence of chitosan on cyclodextrin complexing and solubilizing abilities towards drugs

The present work was performed to investigate the effect of chitosan, a well known hydrophilic polymer with both enhancer and solubilizing properties, on the solubilizing and complexing abilities of cyclodextrins towards drugs. With this aim, phase-solubility studies were carried out with a series of model drugs, both of acid and basic nature and with different water-solubility and lipophilicity values, in the presence of chitosan and cyclodextrin (ß- or hydroxypropyl-ß-cyclodextrin), both separately (binary systems) and in combination (ternary systems). Unexpectedly, differently from the favorable effect reported in literature for various hydrophilic polymers, the addition of chitosan to the cyclodextrin complexation medium caused a decrease in the cyclodextrin complexing power towards all the examined drugs, independent from their very different physicochemical properties. On the contrary, the influence of the polymer on the cyclodextrin solubilizing efficiency was found to be dependent on the type of drug and both positive, or negative or non-significant effects were observed. The overall results are explained in terms of a common basic mechanism due to the presence of chitosan–cyclodextrin interactions, which hindered the drug–cyclodextrin complex formation, thus causing the binding constant reduction; the simultaneous presence of drug–chitosan and/or chitosan–(drug–cyclodextrin complex) interactions, different from drug to drug, were considered responsible for the distinct (and sometimes opposite) effects observed in the drug solubilizing efficiency of ternary systems.