Influence of degree of substitution of cyclodextrins on their colligative properties in solution

The purpose of this study was to investigate the effect of the total degree of substitution (TDS) on the colligative properties of substituted cyclode xtrins (CDs; i.e., beta- and gamma -cyclodextrins substituted with sulfobut ylether or hydroxypropyl groups) in solution. The osmotic pressure (OP) of aqueous CD solutions was determined over the concentration range 100-350 mm ol/kg using vapor pressure osmometry. A chloride ion-selective electrode wa s used to help determine the possible mechanism for any CD-water interactio ns that might occur by measuring the chloride-ion activity of a sodium chlo ride solution containing various CDs. Titration microcalorimetry was used t o verify that sodium chloride did not interact with the CDs, thereby permit ting the chloride ion activity to be utilized as an indicator of any possib le CD-water interaction. The results indicate that CDs with different total degrees of substitution (TDS) exhibit different colligative properties in solution. It was observed that increases in the degree of substitution of t he CD produced an increased OP. All substituted CDs exhibited an OP above t heir theoretical values, whereas the OP of the unsubstituted gamma -CD was below its expected value, likely due to self-association. The results obtai ned with the chloride-ion selective electrode did not exhibit a consistent trend; however, it was observed that changes in the TDS caused significant changes in the activity of chloride ions in solution. These findings are of interest in using CDs to formulate parenteral and ophthalmic solutions whe re the OP of the solutions must be considered. (C) 2001 Wiley-Liss, Inc. an d the American Pharmaceutical Association.