Thoma K, Ziegler I
Department of Pharmaceutical Technology, Ludwig-Maximilians University Munich, Germany.
Drug Dev Ind Pharm. 1998 May;24(5):413-22. doi: 10.3109/03639049809085638.
Three different extruders, the Alexanderwerk gravity-feed roll extruder, the Gabler axial, single-screw extruder, and the NICA radial-screw extruder, were compared for their suitability for different placebo formulations and for fenoldopam pellets. A fourth extruder, the experimental ram extruder, was also included in some of the comparisons. The successful spheronization of extrudates from each of these extruders requires the correct water content. This water content, however, is different for each of the formulations and for each extruder. Generally, the Gabler unit required the highest amounts of water for a successful spheronization, yielding > or = 90% between 710 and 1250 microns. The NICA unit needed much less water for the same formulation, and the Alexanderwerk unit required even less water than the NICA unit. Pellet sphericity was also strongly dependent on the correct water content of formulations, but was generally better for pellets produced with the Alexanderwerk or NICA units. A two-way ANOVA test for the individual formulations showed a significant difference in the mean particle size of batches produced with the NICA or the Alexanderwerk and the Gabler extruder. No significant differences could be found between any of the Alexanderwerk or NICA batches. Both extruders showed a linear dependence of the mean particle size on the water content of formulations, but the Gabler extruder showed an almost unchanged particle size over a wide range of water contents, provided that the formulation could be extruded successfully. Batches that were extruded on the NICA unit showed a significantly lower bulk density than comparable Alexanderwerk or Gabler batches. Comparing the true density of pellets, we found that significant differences could only be stated for Avicel PH 101 + water batches and only for the NICA/Gabler interaction. True density increased for all three extruders with increasing amounts of soluble components and with increasing water content. The NICA batches also exhibited a significant difference of the Hausner factor from the other two extruders, but no differences could be found in the friability of pellets.
比较了三种不同的挤出机，即亚历山大韦克重力进料辊式挤出机、加布勒轴向单螺杆挤出机和尼卡径向螺杆挤出机，以评估它们对不同安慰剂配方和非诺多泮微丸的适用性。在一些比较中还包括了第四种挤出机，即实验性冲压挤出机。要使这些挤出机各自的挤出物成功滚圆成球，都需要正确的含水量。然而，每种配方和每种挤出机所需的含水量各不相同。一般来说，加布勒设备成功滚圆成球所需的水量最多，在710至1250微米之间可得到≥90%的微丸。对于相同配方，尼卡设备所需的水量要少得多，而亚历山大韦克设备所需的水量甚至比尼卡设备还要少。微丸的球形度也强烈依赖于配方的正确含水量，但用亚历山大韦克或尼卡设备生产的微丸通常球形度更好。对各个配方进行的双向方差分析表明，用尼卡或亚历山大韦克挤出机以及加布勒挤出机生产的批次，其平均粒径存在显著差异。在亚历山大韦克或尼卡的任何批次之间均未发现显著差异。两种挤出机的平均粒径均与配方的含水量呈线性相关，但加布勒挤出机在很宽的含水量范围内粒径几乎不变，前提是该配方能够成功挤出。在尼卡设备上挤出的批次其堆积密度明显低于可比的亚历山大韦克或加布勒批次。比较微丸的真密度时，我们发现仅在微晶纤维素PH 101+水批次中，且仅在尼卡/加布勒相互作用方面存在显著差异。随着可溶性成分含量的增加以及含水量的增加，所有三种挤出机生产的微丸真密度均升高。尼卡批次的豪斯纳因数与其他两种挤出机也存在显著差异，但在微丸的脆碎度方面未发现差异。
