Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka.
Chem Pharm Bull (Tokyo). 2023;71(6):428-434. doi: 10.1248/cpb.c23-00045.
In planetary centrifugal wet granulation, the binder is often mixed into the formulation as a powder, followed by the addition of a wetting liquid, in a single step. Therefore, the amount and dispersion of the wetting liquid are important factors that determining granulation success and granules characteristics. In this study, granulation experiments, according to the Box-Behnken design, were performed. Further, the effects of equipment parameters, namely, processing speed, processing time, and vessel size, on the minimum amount of wetting liquid required to enable granulation and dispersion state in the vessel were statistically analyzed. Placebo granules were formulated with lactose hydrate and corn starch (7 : 3), using sodium carmellose as a binder. Results showed that the amount of wetting liquid decreased with increase in processing speed, processing time, and vessel size; however, the dispersion state of the wetting liquid was not significantly affected. Analysis of the effects of the equipment parameters on granule characteristics showed that a larger vessel size was proportional to a larger median diameter and smaller particle-size distribution width (span), and a faster processing speed was proportional to a smaller span. Furthermore, granules with the target properties could be prepared according to the parameters estimated from the model. In conclusion, the equipment parameters for controlling the amount of wetting liquid, which affected the granule properties, were clarified.
在行星离心湿法造粒中,粘合剂通常作为粉末混入配方中,然后加入润湿液,一步完成。因此,润湿液的用量和分散性是决定造粒成功和颗粒特性的重要因素。本研究采用 Box-Behnken 设计进行了造粒实验,并对设备参数(即处理速度、处理时间和容器尺寸)对造粒所需的最小润湿液用量和容器内润湿液分散状态的影响进行了统计分析。采用乳糖一水合物和玉米淀粉(7∶3)作为填充剂,用羧甲基纤维素钠作为粘合剂制备了安慰剂颗粒。结果表明,随着处理速度、处理时间和容器尺寸的增加,润湿液的用量减少,但润湿液的分散状态没有显著影响。对设备参数对颗粒特性的影响进行分析表明,较大的容器尺寸与较大的中值粒径和较小的粒径分布宽度(跨度)成正比,较快的处理速度与较小的跨度成正比。此外,根据模型估计的参数可以制备出具有目标特性的颗粒。总之,确定了控制润湿液用量的设备参数,这些参数影响颗粒特性。