Beten D B, Amighi K, Moës A J
Laboratoire de Pharmacie Galénique et de Biopharmacie, Université Libre de Bruxelles, Belgium.
Pharm Res. 1995 Sep;12(9):1269-72. doi: 10.1023/a:1016253119194.
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.
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.
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.
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.
本研究的目的是证明在工业规模上制备控释药物-聚合物共蒸发物是可行的，避免了采用传统溶剂蒸发技术制备共蒸发物时遇到的回收问题以及研磨和筛分过程。
采用流化床包衣法将双嘧达莫-尤特奇共混物的有机溶液喷雾到中性丸粒上，制备控释共蒸发物。选用肠溶丙烯酸聚合物尤特奇L100-55、L和S作为分散剂，所有制剂均选择药物/聚合物比例为2:8。采用偏光显微镜、X射线衍射光谱和差示扫描量热法来确定药物在包衣膜中是无定形还是结晶形。此外，对双嘧达莫包衣丸粒在模拟胃肠道pH变化的试验介质中进行体外溶出试验，并将结果与通过传统溶剂蒸发法制备的共蒸发物的释放数据进行比较。
所有结果均清楚表明，双嘧达莫在沉积于中性丸粒上的包衣膜中以及通过传统溶剂蒸发法获得的共蒸发物颗粒中均为无定形。当将双嘧达莫包衣丸粒的释放模式与用相同肠溶丙烯酸聚合物制备的药物共蒸发物颗粒的释放模式进行比较时，结果显示出相似的溶出趋势。
所得结果表明，基于无定形固体分散体的形成，制粒可被视为中试工厂和/或大规模生产控释剂型的一种首选方法。
