The 3D printing has become important in drug development for patient-centric therapy by combining multiple drugs with different release characteristics in a single polypill. This study explores the critical formulation and geometric variables for tailoring the release of Atorvastatin and Metoprolol as model drugs in a polypill when manufactured via pressure-assisted-microextrusion 3D printing technology. The effects of these variables on the extrudability of printing materials, drug release and other quality characteristics of polypills were studied employing a definitive screening design. The extrudability of printing materials was evaluated in terms of flow pressure, non-recoverable strain, compression rate, and elastic/plastic flow. The extrudability results helped in defining an operating space free of printing defects. The Atorvastatin compartment of polypill consisted of mesh-shaped layers while Metoprolol compartment consisted of a core surrounded by a release controlling shell with a hydrophobic septum between the two compartments.

The results indicated that both the formulation and geometric variables govern the drug release of the polypill. Specifically, the use of HPMC E3 matrix, and a 2 mm distance between the strands at a weaving angle of 90° were critical in achieving the desired immediate-release profile of Atorvastatin. The core and shell design primarily determined the desired extended-release profile of Metoprolol. The carbopol and HPMC K100 concentration of 1% in the core and 10% in the shell and the number of shell layers in Metoprolol compartment were critical for achieving the desired Metoprolol dissolution. Polymer and Metoprolol content of the shell and shell-thickness affected the mechanical strength of the polypills. In conclusion, the 3D printing provides the flexibility for independently tailoring the release of different drugs in the same dosage form for patient centric therapy, and both the formulation and geometric parameters need to be optimized to achieve desired drug release.

通过将多种具有不同释放特性的药物组合在一个复方药丸中，3D 打印在以患者为中心的治疗药物开发中变得非常重要。本研究探讨了在通过压力辅助微挤出 3D 打印技术制造时，用于定制阿托伐他汀和美托洛尔作为模型药物在复方药丸中的释放的关键配方和几何变量。采用明确的筛选设计研究了这些变量对印刷材料的可挤出性、药物释放和多丸的其他质量特征的影响。印刷材料的可挤出性通过流动压力、不可恢复应变、压缩率和弹性/塑性流动来评估。可挤出性结果有助于确定没有印刷缺陷的操作空间。

结果表明，配方和几何变量都控制着复方药丸的药物释放。具体来说，使用 HPMC E3 基质，以及在 90° 编织角的股线之间有 2 毫米的距离对于实现所需的阿托伐他汀速释曲线至关重要。核心和外壳设计主要决定了美托洛尔所需的缓释曲线。核心中 1% 和壳中 10% 的卡波普和 HPMC K100 浓度以及美托洛尔隔室中的壳层数对于实现所需的美托洛尔溶出度至关重要。壳的聚合物和美托洛尔含量和壳厚度影响复合丸的机械强度。综上所述，