Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Gründenstr. 40, CH-4132, Muttenz, Switzerland.
AAPS PharmSciTech. 2011 Mar;12(1):323-30. doi: 10.1208/s12249-011-9589-y. Epub 2011 Feb 1.
These days an alternative to soft capsules is liquid-filled hard capsules. Their filling technology was investigated earlier with highly viscous formulations, while hardly any academic research focused on low-viscosity systems. Accordingly, this work addressed the filling of such oils that are splashing during the dosing process. It was aimed to first study capsule filling, using middle-chain triglycerides as reference oil, in order to then evaluate the concept of a new theoretical splashing degree for different oils. A laboratory-scale filling machine was used that included capsule sealing. Thus, the liquid encapsulation by microspray technology was employed to seal the dosage form. As a result of the study with reference oil, the filling volume and the temperature were found to be significant for the rate of leaking capsules. The filling volume was also important for weight variability of the capsules. However, most critical for this variability was the diameter of the filling nozzle. We proposed a power law for the coefficient of weight variability as a function of the nozzle diameter and the obtained exponent agreed with the proposed theory. Subsequently, a comparison of different oils revealed that the relative splashing degree shared a correlation with the coefficient of the capsule weight variability (Pearson product moment correlation of r=0.990). The novel theoretical concept was therefore found to be predictive for weight variability of the filled capsules. Finally, guidance was provided for the process development of liquid-filled capsules using low-viscosity oils.
如今，一种替代软胶囊的方法是填充液的硬胶囊。此前，人们已经研究了高粘度制剂的填充技术，而几乎没有任何学术研究关注低粘度系统。因此，这项工作针对在给药过程中会飞溅的油类进行了填充研究。首先，使用中链甘油三酯作为参考油来研究胶囊填充，然后评估不同油类新的理论飞溅程度的概念。使用包括胶囊密封的实验室规模填充机，通过微喷技术对剂型进行液体包封。作为参考油研究的结果，发现填充体积和温度对泄漏胶囊的速率有显著影响。填充体积对胶囊重量变化性也很重要。然而，对这种可变性最重要的是灌装喷嘴的直径。我们提出了一个作为喷嘴直径函数的重量变化系数的幂律，所得到的指数与提出的理论一致。随后，对不同油类的比较表明，相对飞溅程度与胶囊重量变化系数之间存在相关性（皮尔逊积矩相关系数 r=0.990）。因此，新的理论概念被发现对填充胶囊的重量变化性具有预测性。最后，为使用低粘度油填充液体制剂的工艺开发提供了指导。
