Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
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DOI：
10.3390/pharmaceutics11120633
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发表时间：
2019-12-01
期刊：
影响因子：
5.4
通讯作者：
Qi, Sheng
中科院分区：
文献类型：
--
作者：
Alhijjaj, Muqdad;Nasereddin, Jehad;Qi, Sheng
熔融沉积成型（FDM）三维（3D）打印作为生产药物固体剂型的直接制造方法正被越来越多地探索。尽管它作为药物制剂工具具有许多优点，但它仍然限于概念验证制剂。为了达到足够的精度和印刷质量，印刷过程的优化仍有待研究。如果FDM从概念验证阶段发展为适用的制药生产工具，那么证明对FDM工艺参数及其对打印剂型质量的影响的透彻理解无疑是必要的。本文描述了对FDM的一些关键工艺参数及其对可定量的药学相关质量指标的影响的研究结果。聚己内酯是既适用于FDM又是GRAS（通常被认为是安全的）材料的少数聚合物之一，用于印刷内部暴露的网格，允许检查FDM的宏观和微观结构再现性。在测量的质量参数中，发现网格的尺寸真实性与目标尺寸匹配不良。发现网格的重量在改变印刷速度时显著变化。印刷温度对重量影响不大。发现每个批次的重量均匀度在可接受的药物质量限度内。此外，我们报告观察到与印刷温度相关的微观结构变形，我们将其称为第一层效应（FLE）。主成分分析（PCA）用于研究因素相互作用，并揭示了重量/剂量准确度和尺寸真实性之间存在相互作用，这表明两个质量参数之间存在折衷。在给定所有感知质量参数和它们之间的必要折衷的情况下，提出了求和标准偏差（SSD）作为提取最佳印刷参数的方法。
Fused deposition modeling (FDM) three-dimensional (3D) printing is being increasingly explored as a direct manufacturing method to product pharmaceutical solid dosage forms. Despite its many advantages as a pharmaceutical formulation tool, it remains restricted to proof-of-concept formulations. The optimization of the printing process in order to achieve adequate precision and printing quality remains to be investigated. Demonstrating a thorough understanding of the process parameters of FDM and their impact on the quality of printed dosage forms is undoubtedly necessary should FDM advance from a proof-of-concept stage to an adapted pharmaceutical manufacturing tool. This article describes the findings of an investigation into a number of critical process parameters of FDM and their impact on quantifiable, pharmaceutically-relevant measures of quality. Polycaprolactone, one of the few polymers which is both suitable for FDM and is a GRAS (generally regarded as safe) material, was used to print internally-exposed grids, allowing examination of both their macroscopic and microstructural reproducibility of FDM. Of the measured quality parameters, dimensional authenticity of the grids was found to poorly match the target dimensions. Weights of the grids were found to significantly vary upon altering printing speed. Printing temperature showed little effect on weight. Weight uniformity per batch was found to lie within acceptable pharmaceutical quality limits. Furthermore, we report observing a microstructural distortion relating to printing temperature which we dub The First Layer Effect (FLE). Principal Component Analysis (PCA) was used to study factor interactions and revealed, among others, the existence of an interaction between weight/dosing accuracy and dimensional authenticity dictating a compromise between the two quality parameters. The Summed Standard Deviation (SSD) is proposed as a method to extract the optimum printing parameters given all the perceived quality parameters and the necessary compromises among them.