Pharmaceutical usefulness of hydroxypropylcyclodextrins: "e pluribus unum" is an essential feature

A series of hydroxypropyl-beta-cyclodextrins was prepared by a method that leads to a preferential substitution on the secondary hydroxyls, mainly O-2, of beta-cyclodextrin with (S)-2-hydroxypropyl groups. The series consisted of mixtures of compounds with average degrees of substitution of 8, 3, and 1.6 and of a specially isolated monosubstituted compound; thus, the number of components progressively decreased in this series. The crystallinity in the series increased progressively, the first member being fully amorphous and the last one fully crystalline. All members of the series formed clear aqueous solutions at concentrations of greater than 50.0, 2.0, 0.6, and 0.3%, respectively. Therefore, pharmaceutically useful hydroxypropylcyclodextrin preparations are those containing a large number of chemically individual compounds--a feature resulting in an amorphous state and high water solubility.