Release profile comparison and stability of diltiazem-resin microcapsules in sustained release suspensions.

摘要

A sustained release suspension of diltiazem, a short half-life calcium channel blocker, was developed to reduce frequency of drug administration, ease of dose adjustment and improve patient compliance. In this study, the sustained release of diltiazem was obtained by complexing the drug with Dowex 50W x 4 and Dowex 50W x 8, strong cationic exchange resins with 4% and 8% degree of cross-linking, respectively. The diltiazem-Dowex 50W x 4 complexes provided the highest drug release and were subsequently used to prepare the microcapsules by emulsion-solvent evaporation method, using 0.75-5.00% cellulose acetate butyrate (CAB) in methylene chloride as a coating solution. As the concentration of CAB increased, the size of microcapsule increased and the drug release from the microcapsule was retarded. From release profile comparison using f(1) and f(2) factors, it was found that the microcapsules coated with 1.75% CAB provided a release profile equivalent to the commercial product of diltiazem sustained release capsule, Herbesser 90SR. Furthermore, sustained release suspensions of the diltiazem microcapsules were formulated with the use of 0.8% sodium carboxymethylcellulose or 0.4% xanthan gum as a suspending agent. The suspension of 0.4% xanthan gum showed superior in physical appearance after 120-day storage at 30 and 45 degrees C. In addition, all sustained release suspensions possessed good stability with low drug leaching and their release profiles were unchanged when compared with the dried microcapsules for 120 days at 30 and 45 degrees C.