Muehlenfeld Christian, Thommes Markus
Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany.
J Pharm Pharmacol. 2014 Dec;66(12):1667-76. doi: 10.1111/jphp.12301. Epub 2014 Sep 1.
The aim of this work was to evaluate a continuous, small-scale extrusion process with a particular focus on powder and liquid-feeding systems, because it is likely that uniformity issues are related to small-scale production.
The study is divided into three parts. The first part investigates the uniformity and accuracy of the powder and the liquid feeders. In the second part, a solid polymer and low amounts of liquid plasticizer were combined in hot-melt extrusion. The third part deals with wet extrusion-spheronization using water as the granulation liquid.
The powder and the liquid feed rate were identified as crucial parameters in small-scale extrusion. With respect to powder feeding, the cohesiveness of the powder and electrostatic charging are the limitations, while liquid feeding is challenging based on particularly low feed rates. The hot-melt extrusion was performed using a powder feed rate of 2 g/min. When small quantities of plasticizer were applied to the hot melt extrusions (from 2.5% to 15% w/w), homogenous plasticizer distribution was found. In wet extrusion, larger quantities of water were used and the extrudates were investigated with respect to their spheronization behaviour. Spherical pellets were obtained at certain water contents.
These findings demonstrated that the extruder is a useful tool to screen formulations and perform feasibility studies on a small scale in the early stages of product development.
本研究旨在评估一种连续的小规模挤出工艺,特别关注粉末和液体进料系统,因为均匀性问题可能与小规模生产有关。
该研究分为三个部分。第一部分研究粉末和液体进料器的均匀性和准确性。第二部分,将固体聚合物和少量液体增塑剂在热熔挤出中混合。第三部分涉及以水作为制粒液体的湿挤出滚圆法。
粉末和液体进料速率被确定为小规模挤出中的关键参数。对于粉末进料,粉末的内聚性和静电充电是限制因素,而液体进料由于进料速率特别低而具有挑战性。热熔挤出以2克/分钟的粉末进料速率进行。当向热熔挤出物中加入少量增塑剂(2.5%至15% w/w)时,发现增塑剂分布均匀。在湿挤出中,使用了大量的水,并研究了挤出物的滚圆行为。在特定含水量下获得了球形颗粒。
这些发现表明,挤出机是一种有用的工具,可用于在产品开发的早期阶段小规模筛选配方并进行可行性研究。