Preparation of controlled-release coevaporates of dipyridamole by loading neutral pellets in a fluidized-bed coating system.
OBJECTIVE
The purpose of this study was to demonstrate that it is possible to prepare controlled-release drug-polymer coevaporates on an industrial scale, omitting the recovery problems and the milling and sieving processes encountered when coevaporates are prepared by the conventional solvent-evaporation technique.


METHODS
Controlled-release coevaporates were prepared by spraying organic solutions of dipyridamole-Eudragit blends onto neutral pellets using the fluidized-bed coating method. Enteric acrylic polymers Eudragit L100-55, L, and S were used as dispersing agents and drug/polymer ratio 2:8 was selected for all formulations. Polarized light microscopy, X-ray diffraction spectroscopy, and differential scanning calorimetry were used to determine whether the drug was amorphous or crystalline in the coating films. Moreover, in vitro dissolution tests were performed on the dipyridamole coated pellets in test media simulating the pH variations in the GI tract and the results were compared to the release data obtained from coevaporates prepared by the conventional solvent-evaporation method.


RESULTS
All the results clearly indicate that dipyridamole is amorphous in the coating films deposited on neutral pellets as well as in coevaporate particles obtained by the conventional solvent-evaporation method. When the release patterns of the dipyridamole coated pellets are compared 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 production of controlled-release dosage forms based on the formation of amorphous solid dispersions.
Beten
D B
DB
Laboratoire de Pharmacie Galénique et de Biopharmacie, Université Libre de Bruxelles, Belgium.
Amighi
K
K
Moës
A J
AJ
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000302:isolation & purification*; D004176:Dipyridamole / Q000737:chemistry / Q000302:isolation & purification*; D004339:Drug Compounding / Q000379:methods*; D005069:Evaluation Studies as Topic; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011109:Polymethacrylic Acids / Q000302:isolation & purification; D012996:Solutions; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical; D014961:X-Ray Diffraction
D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D012996:Solutions; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; D004176:Dipyridamole