Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Duesseldorf, Germany.
Pharm Dev Technol. 2013 Feb;18(1):225-35. doi: 10.3109/10837450.2012.700935. Epub 2012 Jul 11.
κ-Carrageenan has been suggested as a pelletisation aid for wet-extrusion/spheronization processes for several years. Until now there have been no systematic investigations regarding process development and stability for long-term production. The aim of this study was to develop a high drug-loaded pellet formulation with κ-carrageenan, so that a robust process cycle occurred over the course of several hours. Binary mixtures of κ-carrageenan and theophylline monohydrate were used and the drug content was varied from 90 to 95%. A twin-screw extruder was used; the power consumption and feed rates were recorded. The pellets were characterized by aspect ratio, diameter, 10% interval, tensile strength and dissolution behavior. The process ran on two occasions for 4.5 h each time. During the extrusion process neither the power consumption nor the feed rates differed significantly, so there was no need to stop the process or change the extrusion parameters. Regarding the spheronization, a cleaning of the spheroniser friction plate was necessary every five batches due to packing of the material on this plate. Overall the resulting pellets showed reproducible and adequate qualities regarding all investigated properties. In conclusion a robust pelletisation process over several hours could be verified. It was possible to produce 42 kg of pellets with adequate properties, without any problems during the process.
κ-卡拉胶多年来一直被提议作为湿法挤压/制球工艺的制粒助剂。到目前为止，还没有关于长期生产的工艺开发和稳定性的系统研究。本研究的目的是开发一种具有κ-卡拉胶的高载药量的丸粒制剂，从而在数小时的过程中实现稳定的工艺循环。使用κ-卡拉胶和一水茶碱的二元混合物，并将药物含量从 90%变化至 95%。使用双螺杆挤出机；记录功率消耗和给料速率。通过形状比、直径、10%间隔、拉伸强度和溶解行为来表征丸粒。该过程进行了两次，每次 4.5 小时。在挤出过程中，功率消耗和给料速率都没有显著差异，因此无需停止该过程或改变挤出参数。至于制球，由于该摩擦板上的物料堆积，需要每五个批次清洁一次制球器的摩擦板。总体而言，所得丸粒在所有研究的性质方面表现出可重复和足够的质量。总之，验证了数小时内的稳定制粒过程。在没有任何问题的情况下，成功地生产了 42 公斤具有适当性能的丸粒。
