Laboratory of Pharmaceutical Technology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
Department of Mechanical and Industrial Design Engineering, TEI of Western Macedonia, Kozani, Greece.
Eur J Pharm Sci. 2018 Jul 30;120:40-52. doi: 10.1016/j.ejps.2018.04.020. Epub 2018 Apr 17.
Fused Deposition Modelling (a.k.a. FDM-3D printing) has been previously employed in the development of personalized medicines with unique properties and release behavior. In the present work, a bilayer dosage form containing two anti-diabetic drugs with different daily dosage regimens; i.e. metformin and glimepiride, was manufactured via FDM 3D printing, studied using a variety of techniques and characterized in vitro. Metformin and glimepiride were embedded in Eudragit® RL sustained release layer and polyvinyl alcohol (PVA) layer respectively. Incorporation of more than one API's into the formulation is desirable, as it increases patient compliance and reduces cost of treatment, especially when distinct dosages of API's can be adjusted individually in situ, in order to meet each patient's specific needs, a capability provided by 3D printing. A number of different preparation methods, which involved different plasticizers and extruders, were tested on manufacturing Eudragit® RL drug-loaded filaments for printing the sustained release layer. The properties of the produced filaments were assessed by means of mechanical and physicochemical characterization techniques and the filaments with the optimum properties were used for printing. Microfocus computed tomography (μCT) imaging-based actual/nominal comparison analysis showed a printing accuracy ranging between -100, +200 μm, while X-ray (XRD) diffractograms revealed the incorporation of the (initially crystalline) API's as amorphous dispersions into polymer matrices. Dissolution tests showed sufficient drug release for both drugs in desired time frames (75 min for glimepiride and 480 min for metformin). The results from the current study emphasize the potentiality of 3D printing technology for tailor-made solid dosage forms for combined pharmacotherapy, even at the cases when API's with different desirable release profiles are employed.
熔融沉积成型（也称为 FDM-3D 打印）已被用于开发具有独特性质和释放行为的个性化药物。在本工作中，通过 FDM 3D 打印制造了包含两种不同日剂量方案的抗糖尿病药物的双层剂型；即二甲双胍和格列美脲，使用多种技术进行了研究，并进行了体外表征。二甲双胍和格列美脲分别嵌入到 Eudragit® RL 缓释层和聚乙烯醇（PVA）层中。将一种以上的 API 纳入制剂中是可取的，因为它可以提高患者的依从性并降低治疗成本，尤其是当可以单独调整不同剂量的 API 以满足每个患者的特定需求时，这是 3D 打印提供的一种能力。测试了许多不同的制备方法，这些方法涉及不同的增塑剂和挤出机，用于制造用于打印缓释层的载有 Eudragit® RL 药物的长丝。通过机械和物理化学特性评估了所生产长丝的特性，并使用具有最佳特性的长丝进行打印。基于微焦点计算机断层扫描（μCT）成像的实际/名义比较分析显示打印精度在-100，+200 μm 之间，而 X 射线（XRD）衍射图显示将（最初为结晶的）API 作为无定形分散体掺入聚合物基质中。溶出度测试表明两种药物在所需时间范围内均有足够的药物释放（格列美脲为 75 分钟，二甲双胍为 480 分钟）。本研究的结果强调了 3D 打印技术用于定制组合药物治疗的固体剂型的潜力，即使在使用具有不同理想释放曲线的 API 的情况下也是如此。
