Comparison in toxicity and solubilizing capacity of hydroxypropyl-ß-cyclodextrin with different degree of substitution.

ABSTRACT

Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) has been widely used as an effective solubilizing agent in pharmaceutical industry for many years. However, the effect of degree of substitution (D.S.) of HP-ß-CD on solubilizing capacity and toxicity has not been concerned. In this study, solubilizing capacity of HP-ß-CDs with three different D.S. (4.55, 6.16 and 7.76) for 16 drugs were measured and their toxicities were compared by a 7-day i.v. administration (q.d.) study in rats. Generally, HP-ß-CD with high D.S. (7.76) showed weaker solubilizing capacity for steroids and BCS class II drugs, but lower hemolytic activity, compared with that of HP-ß-CD with low (4.55) or medium (6.16) D.S. HP-ß-CD with low D.S. resulted in more changes in hematological and biochemical parameters, but the effects were reversible after a 7-day recovery. Moreover, HP-ß-CD with medium D.S. may have slightly greater nephrotoxicity than the other two HP-ß-CDs. HP-ß-CDs with different D.S. had similar urine excretion percentage after i.v. administration and none of them was found to affect glomerular filtration function of rats. The results suggest that HP-ß-CD with low D.S. would be a better choice considering both the solubilizing capacity and toxicity. However, comparison in toxicity of HP-ß-CDs with different D.S. should be carried out in human in view of its species-dependence property.