Lamrabet Nabil, Hess Florian, Leidig Philip, Marx Andreas, Kipping Thomas
Merck Life Science KGaA, Frankfurter Straße 250, 64293 Darmstadt, Germany.
Department of Biopharmaceutic and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17487 Greifswald, Germany.
Pharmaceutics. 2024 Nov 22;16(12):1501. doi: 10.3390/pharmaceutics16121501.
Melt-based 3D printing technologies are currently extensively evaluated for research purposes as well as for industrial applications. Classical approaches often require intermediates, which can pose a risk to stability and add additional complexity to the process. The Advanced Melt Drop Deposition (AMDD) technology, is a 3D printing process that combines the principles of melt extrusion with pressure-driven ejection, similar to injection molding. This method offers several advantages over traditional melt-based 3D printing techniques, making it particularly suitable for pharmaceutical applications. This study evaluates the AMDD printing system for producing solid oral dosage forms, with a primary focus on the thermo-stable polymer polyvinyl alcohol (PVA). The suitability of AMDD technology for creating amorphous solid dispersions (ASDs) is also examined. Finally, the study aims to define the material requirements and limitations of the raw materials used in the process. The active pharmaceutical ingredients (APIs) indometacin and ketoconazole were used, with PVA 4-88 serving as the carrier polymer. Powders, wet granulates, and pellets were investigated as raw materials and characterized. Dissolution testing and content analyses were performed on the printed dosage forms. Solid-state characterization was conducted using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Degradation due to thermal and mechanical stress was analyzed using nuclear magnetic resonance spectroscopy (NMR). The results demonstrate that the AMDD 3D printing process is well-suited for producing solid dosage forms. Tablets were successfully printed, meeting mass uniformity standards. Adjusting the infill volume from 30% to 100% effectively controlled the drug release rate of the tablets. Solid-state analysis revealed that the AMDD process can produce amorphous solid dispersions with enhanced solubility compared to their crystalline form. The experiments also demonstrated that powders with a particle size of approximately 200 µm can be directly processed using AMDD technology.
基于熔融的3D打印技术目前正被广泛评估用于研究目的以及工业应用。传统方法通常需要中间体，这可能对稳定性构成风险并给工艺增加额外的复杂性。先进熔融液滴沉积（AMDD）技术是一种3D打印工艺，它将熔融挤出原理与压力驱动喷射相结合，类似于注塑成型。与传统的基于熔融的3D打印技术相比，这种方法具有几个优点，使其特别适用于药物应用。本研究评估了用于生产固体口服剂型的AMDD打印系统，主要关注热稳定聚合物聚乙烯醇（PVA）。还研究了AMDD技术用于制备无定形固体分散体（ASD）的适用性。最后，该研究旨在确定该工艺中使用的原材料的材料要求和局限性。使用了活性药物成分（API）吲哚美辛和酮康唑，以PVA 4 - 88作为载体聚合物。对粉末、湿颗粒和丸粒作为原材料进行了研究并进行了表征。对打印的剂型进行了溶出度测试和含量分析。使用差示扫描量热法（DSC）和X射线衍射（XRD）进行了固态表征。使用核磁共振光谱（NMR）分析了热和机械应力导致的降解。结果表明，AMDD 3D打印工艺非常适合生产固体剂型。成功打印出符合质量均匀性标准的片剂。将填充体积从30%调整到100%有效地控制了片剂的药物释放速率。固态分析表明，与结晶形式相比，AMDD工艺可以生产出溶解度增强的无定形固体分散体。实验还表明，粒径约为200 µm的粉末可以使用AMDD技术直接加工。
