SLOW-RELEASE CHARACTERISTICS OF DILTIAZEM FROM ETHYLATED BETA-CYCLODEXTRIN COMPLEXES

Release characteristics of two ethylated β‐cyclodextrins [heptakis(2, 6‐di‐O‐ethyl)‐β‐cyclodextrin (diethyl‐β‐cyclodextrin) and heptakis(2, 3, 6‐tri‐O‐ethyl)‐β‐cyclodextrin (triethyl‐β‐cyclodextrin)] as sustained‐release drug carriers were evaluated using diltiazem hydrochloride, a water‐soluble calcium antagonist. The release rate of diltiazem from compressed tablets was significantly retarded by the complexation with ethylated β‐cyclodextrin. Various environmental effects (such as pH, rotating speed, and additive in the dissolution medium) on the release rate were investigated, together with a microscopic observation of the tablet surface. The water penetration rate into the tablet was measured in order to gain insight into the release mechanism. The results suggested that diltiazem is released slowly from the hydrophobic matrix consisting of diethyl‐β‐cyclodextrin following water penetration. When a single dose of tablets containing diethyl‐β‐cyclodextrin complex was orally administered to dogs, the sustained‐release pattern of the drug, without decrease in area under the plasma concentration–time curve, was produced for a long period. The release rate of diltiazem can be controlled by combining the ethylated β‐cyclodextrin complexes with the parent β‐cyclodextrin complex in different mixing ratios. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company