Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD, USA.
Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, MD, USA.
Int J Pharm. 2022 Apr 5;617:121599. doi: 10.1016/j.ijpharm.2022.121599. Epub 2022 Feb 16.
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.
3D 打印技术在以患者为中心的治疗中变得越来越重要，它可以将具有不同释放特性的多种药物结合在一个单一的多颗粒片中。本研究探索了通过压力辅助微挤出 3D 打印技术制造多颗粒片时，调整阿托伐他汀和酒石酸美托洛尔作为模型药物释放的关键配方和几何变量。使用确定筛选设计研究了这些变量对打印材料挤出性、药物释放和多颗粒片其他质量特性的影响。打印材料的挤出性通过流动压力、不可恢复应变、压缩率和弹塑性流动来评估。挤出性结果有助于定义无打印缺陷的操作空间。多颗粒片中阿托伐他汀部分由网状层组成，而美托洛尔部分由核心组成，核心周围是一个控释壳，两个部分之间有一个疏水隔片。结果表明，配方和几何变量都控制着多颗粒片的药物释放。具体来说，使用 HPMC E3 基质和编织角为 90°时 2mm 的丝间距对于实现阿托伐他汀的期望即时释放特性至关重要。核心和壳设计主要决定了美托洛尔的期望延长释放特性。核心中美托洛尔的 Carbopol 和 HPMC K100 浓度为 1%，壳中为 10%，美托洛尔部分的壳层数为 3 层，对于实现期望的美托洛尔溶解度至关重要。壳和壳层厚度中的聚合物和美托洛尔含量会影响多颗粒片的机械强度。总之，3D 打印为以患者为中心的治疗提供了在同一剂型中独立调整不同药物释放的灵活性，需要优化配方和几何参数以实现期望的药物释放。
