UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
FabRx Ltd., 3 Romney Road, Ashford, Kent TN24 0RW, UK.
Int J Pharm. 2020 Mar 15;577:119066. doi: 10.1016/j.ijpharm.2020.119066. Epub 2020 Jan 23.
Three-dimensional printing (3DP) is a revolutionary technology in pharmaceuticals, enabling the personalisation of flexible-dose drug products and 3D printed polypills (polyprintlets). A major barrier to entry of this technology is the lack of non-destructive quality control methods capable of verifying the dosage of multiple drugs in polyprintlets at the point of dispensing. In the present study, 3D printed films and cylindrical polyprintlets were loaded with flexible, therapeutic dosages of two distinct drugs (amlodipine and lisinopril) across concentration ranges of 1-5% w/w and 2-10% w/w, respectively. The polyprintlets were non-destructively analysed for dose content using a portable near infrared (NIR) spectrometer and validated calibration models were developed using partial least squares (PLS) regression, which showed excellent linearity (R Pred = 0.997, 0.991), accuracy (RMSEP = 0.24%, 0.24%) and specificity (LV1 = 82.77%, 79.55%) for amlodipine and lisinopril, respectively. X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA) showed that sintering partially transformed the phase of both drugs from the crystalline to amorphous forms. For the first time, we report a non-destructive method for quality control of two separate active ingredients in a single 3D printed drug product using NIR spectroscopy, overcoming a major barrier to the integration of 3D printing into clinical practice.
三维打印（3DP）是制药领域的一项革命性技术，能够实现灵活剂量药物产品和 3D 打印多丸（polyprintlets）的个性化定制。该技术进入市场的主要障碍是缺乏能够在配药点验证多丸中多种药物剂量的非破坏性质量控制方法。在本研究中，3D 打印薄膜和圆柱形多丸分别以 1-5%w/w 和 2-10%w/w 的浓度范围负载两种不同药物（氨氯地平和赖诺普利）的灵活治疗剂量。使用便携式近红外（NIR）光谱仪对多丸进行非破坏性剂量含量分析，并使用偏最小二乘（PLS）回归建立验证校准模型，结果显示氨氯地平和赖诺普利的线性度（R Pred = 0.997，0.991）、准确性（RMSEP = 0.24%，0.24%）和特异性（LV1 = 82.77%，79.55%）均非常出色。X 射线粉末衍射（XRPD）和热重分析（TGA）表明，烧结过程使两种药物的晶相部分转变为无定形形式。我们首次报道了一种使用 NIR 光谱法对单一 3D 打印药物产品中两种单独活性成分进行非破坏性质量控制的方法，克服了将 3D 打印技术集成到临床实践中的主要障碍。
