Digkas Tryfon, Porfire Alina, Van Renterghem Jeroen, Samaro Aseel, Borodi Gheorghe, Vervaet Chris, Crișan Andrea Gabriela, Iurian Sonia, De Beer Thomas, Tomuta Ioan
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy "Iuliu Hațieganu", 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania.
Pharmaceuticals (Basel). 2023 Jul 26;16(8):1062. doi: 10.3390/ph16081062.
The present study aimed to develop 3D printed dosage forms, using custom-made filaments loaded with diclofenac sodium (DS). The printed tablets were developed by implementing a quality by design (QbD) approach. Filaments with adequate FDM 3D printing characteristics were produced via hot melt extrusion (HME). Their formulation included DS as active substance, polyvinyl alcohol (PVA) as a polymer, different types of plasticisers (mannitol, erythritol, isomalt, maltodextrin and PEG) and superdisintegrants (crospovidone and croscarmellose sodium). The physicochemical and mechanical properties of the extruded filaments were investigated through differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile measurements. In addition, cylindrical-shaped and tubular-shaped 3D dosage forms were printed, and their dissolution behaviour was assessed via various drug release kinetic models. DSC and XRD results demonstrated the amorphous dispersion of DS into the polymeric filaments. Moreover, the 3D printed tablets, regardless of their composition, exhibited a DS release of nearly 90% after 45 min at pH 6.8, while their release behaviour was effectively described by the Korsmeyer-Peppas model. Notably, the novel tube design, which was anticipated to increase the drug release rate, proved the opposite based on the dissolution study results. Additionally, the use of crospovidone increased DS release rate, whereas croscarmellose sodium decreased it.
本研究旨在使用负载双氯芬酸钠（DS）的定制长丝开发3D打印剂型。通过实施质量源于设计（QbD）方法来开发打印片剂。具有适当熔融沉积成型（FDM）3D打印特性的长丝通过热熔挤出（HME）制备。其配方包括作为活性物质的DS、作为聚合物的聚乙烯醇（PVA）、不同类型的增塑剂（甘露醇、赤藓糖醇、异麦芽酮糖醇、麦芽糊精和聚乙二醇）以及超级崩解剂（交联聚维酮和交联羧甲基纤维素钠）。通过差示扫描量热法（DSC）、X射线衍射（XRD）和拉伸测量研究了挤出长丝的物理化学和机械性能。此外，打印了圆柱形和管状3D剂型，并通过各种药物释放动力学模型评估了它们的溶出行为。DSC和XRD结果表明DS在聚合物长丝中呈无定形分散。此外，无论其组成如何，3D打印片剂在pH 6.8条件下45分钟后DS释放率接近90%，而其释放行为可用Korsmeyer-Peppas模型有效描述。值得注意的是，预期会提高药物释放速率的新型管状设计，根据溶出研究结果却得出了相反的结论。此外，使用交联聚维酮提高了DS释放速率，而交联羧甲基纤维素钠则降低了DS释放速率。
