Development of pellet coating tehnique using electrostati enhanced fluidized bed

Fluidized bed has been used in the pharmaceutical industry for drying and coating products. The present study was aimed to develop pellet coating technique using electrostatic enhanced fluidized bed and investigate the effect of process variables on the coating efficiency and physicochemical properties of coated pellets. The variables studied were types of drug core pellets, film formers and electrical potential applied to the nozzle. Propranolol hydrochloride and diclofenac sodium pellets (50 %w/w) were prepared by extrusion-spheronization technique and used as the core pellets. The core pellets was coated with either the aqueous solution of hydroxypropylmethylcellulose or ethylcellulose aqueous dispersion. Electrical potential was applied to the nozzle at the magnitude of 4 kV. The resulting coated pellets were compared with those obtained from the conventional technique, i.e. fluidized bed with non-applied electrical potential. It was found that the coated pellets remained round shaped and free-flowing. The coating of diclofenac sodium core pellets resulted in homogeneous film regardless of the effect of coating conditions. In all cases, an image analysis showed that the film thickness was significantly influenced by types of drug core pellets and applied electrical potential (p<0.05). However, applying charged droplets to core pellets was not proved to significantly enhanced the coating efficiency (p>0.05) but rather improved its reproducibility. The drug released was primarily controlled by types of film former, although there were some influences from other process variables. The results showed that, no matter how complex the nature of electrostatic fluidized bed coating was, this technique may be useful for pharmaceuticals when process variables are carefully controlled.流化床（Fluidized bed）已广泛应用于制药工业，用于产品的干燥与包衣工序。本研究旨在开发静电强化流化床包衣技术，并考察工艺变量对包衣效率及包衣微丸理化性质的影响。本次考察的变量包括药物核心微丸类型、成膜材料种类，以及施加于喷嘴的电势。采用挤出滚圆法制备了质量分数为50%的盐酸普萘洛尔与双氯芬酸钠微丸，将其作为核心微丸。核心微丸分别以羟丙基甲基纤维素水溶液或乙基纤维素水分散体进行包衣。喷嘴处施加的电势幅值为4 kV。将所得包衣微丸与传统工艺（即未施加电势的流化床工艺）制备的产物进行对比。结果显示，包衣后的微丸仍保持球形且具有良好的自由流动性。双氯芬酸钠核心微丸的包衣膜均一性优异，不受包衣工艺条件的影响。经图像分析可知，所有实验条件下，包衣膜厚度均显著受药物核心微丸类型与施加电势的影响（p<0.05）。不过，向核心微丸施加带电液滴并未被证实可显著提升包衣效率（p>0.05），反而改善了包衣过程的重现性。药物释放行为主要受成膜材料类型调控，尽管其他工艺变量也存在一定影响。研究结果表明，无论静电流化床包衣技术的内在机制多么复杂，只要谨慎调控工艺变量，该技术即可在制药领域具备应用价值。