Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010 Graz, Austria.
Int J Pharm. 2016 Jun 15;506(1-2):35-45. doi: 10.1016/j.ijpharm.2016.04.029. Epub 2016 Apr 14.
Previously, we introduced a one-step nano-extrusion (NANEX) process for transferring aqueous nano-suspensions into solid formulations directly in the liquid phase. Nano-suspensions were fed into molten polymers via a side-feeding device and excess water was eliminated via devolatilization. However, the drug content in nano-suspensions is restricted to 30 % (w/w), and obtaining sufficiently high drug loadings in the final formulation requires the processing of high water amounts and thus a fundamental process understanding. To this end, we investigated four polymers with different physicochemical characteristics (Kollidon(®) VA64, Eudragit(®) E PO, HPMCAS and PEG 20000) in terms of their maximum water uptake/removal capacity. Process parameters as throughput and screw speed were adapted and their effect on the mean residence time and filling degree was studied. Additionally, one-dimensional discretization modeling was performed to examine the complex interactions between the screw geometry and the process parameters during water addition/removal. It was established that polymers with a certain water miscibility/solubility can be manufactured via NANEX. Long residence times of the molten polymer in the extruder and low filling degrees in the degassing zone favored the addition/removal of significant amounts of water. The residual moisture content in the final extrudates was comparable to that of extrudates manufactured without water.
此前，我们介绍了一种一步纳米挤压（NANEX）工艺，可将水性纳米混悬液直接在液相中转化为固体制剂。纳米混悬液通过侧进料装置送入熔融聚合物中，并通过脱挥发分除去多余的水。然而，纳米混悬液中的药物含量限制在 30%（w/w），为了在最终制剂中获得足够高的药物载量，需要处理大量的水，因此需要对基本工艺有深入的了解。为此，我们研究了四种具有不同物理化学特性的聚合物（Kollidon® VA64、Eudragit® E PO、HPMCAS 和 PEG 20000），考察了它们的最大水吸收/去除能力。我们调整了工艺参数，如吞吐量和螺杆转速，并研究了它们对平均停留时间和填充度的影响。此外，我们还进行了一维离散化建模，以研究在加水/除水过程中螺杆几何形状和工艺参数之间的复杂相互作用。结果表明，具有一定水溶性/溶解度的聚合物可以通过 NANEX 制造。熔融聚合物在挤出机中的停留时间长，脱气区的填充度低，有利于加入/去除大量的水。最终挤出物中的残留水分含量与未加水制造的挤出物相当。
