PREPARATION OF CONTROLLED-RELEASE COEVAPORATES OF DIPYRIDAMOLE BY LOADING NEUTRAL PELLETS IN A FLUIDIZED-BED COATING SYSTEM

Purpose. The purpose of this study was to demonstrate that it is possi ble to prepare controlled-release drug-polymer coevaporates on an indu strial scale, omitting the recovery problems and the milling and sievi ng processes encountered when coevaporates are prepared by the convent ional solvent-evaporation technique, Methods. Controlled-release coeva porates were prepared by spraying organic solutions of dipyridamole-Eu dragit(R) blends onto neutral pellets using the fluidized-bed coating method. Enteric acrylic polymers Eudragit(R) L100-55, L, and S were us ed as dispersing agents and drug/polymer ratio 2:8 was selected for al l formulations. Polarized light microscopy, X-ray diffraction spectros copy, and differential scanning calorimetry were used to determine whe ther the drug was amorphous or crystalline in the coating films. Moreo ver, in vitro dissolution tests were performed on the dipyridamole coa ted pellets in test media simulating the pH variations in the GI tract and the results were compared to the release data obtained from coeva porates prepared by the conventional solvent-evaporation method. Resul ts. All the results clearly indicate that dipyridamole is amorphous in the coating films deposited on neutral pellets as well as in coevapor ate particles obtained by the conventional solvent-evaporation method. When the release patterns of the dipyridamole coated pellets are comp ared to those of the drug coevaporate particles prepared with the same enteric acrylic polymers, the results show similar dissolution trends . Conclusions. The results obtained indicate that pelletization can be considered as a method of choice for pilot plant and/or full-scale pr oduction of controlled-release dosage forms based on the formation of amorphous solid dispersions.