DRUGS, IN CYCLODEXTRINS, IN LIPOSOMES - A NOVEL-APPROACH TO THE CHEMICAL-STABILITY OF DRUGS SENSITIVE TO HYDROLYSIS

The entrapment in multilamellar liposomes of the inclusion complexes o f cyclodextrins with drugs sensitive to hydrolysis, is being examined. The anti-inflammatory drug indomethacin (IND), rapidly hydrolyzed in alkaline media, can be stabilized 75-fold when its inclusion complex w ith the hydroxypropylated derivative of beta-cyclodextrin (HP beta CD) is entrapped in multilamellar liposomes. These liposomes were compose d of egg phosphatidylcholine and cholesterol of 1:1 molar ratio and we re prepared according to the dehydration-rehydration method. The molar ratio for the IND:HP beta CD inclusion complex was estimated to be 1: 1 using the continuous variation method based on the H-1 NMR data. Fur thermore, the binding constant (K-11) of the IND:HP beta CD complex wa s estimated kinetically and by H-1 NMR. (C) 1998 Elsevier Science B.V. All rights reserved.