Manini Giuseppe, Deldime Maud, Benali Samira, Raquez Jean-Marie, Goole Jonathan
Laboratory of Pharmaceutics and Biopharmaceutics, Université libre de Bruxelles, Campus de la Plaine, CP207, Boulevard du Triomphe, Brussels 1050, Belgium; Laboratory of Polymeric and Composite Materials (LPCM), Center of Innovation and Research in Materials and Polymers (CIRMAP), University of Mons, Place du Parc 23, B-7000 Mons, Belgium.
Laboratory of Pharmaceutics and Biopharmaceutics, Université libre de Bruxelles, Campus de la Plaine, CP207, Boulevard du Triomphe, Brussels 1050, Belgium.
Int J Pharm. 2021 Jun 15;603:120702. doi: 10.1016/j.ijpharm.2021.120702. Epub 2021 May 12.
In this work, the versatility of pressure extrusion-based printing (PEBP) was used as 3D printing process to create long-acting implantable dosage forms. Different release profiles were achieved based on the drug concentration, the way of preparation and the design of the final implants. Polycaprolactone (PCL) was used as the polymer to sustain the release of the loaded drug. Paliperidone palmitate (PP), a BCS Class II drug, used in the treatment of schizophrenia, was used as the model drug. Two PP concentrations (e.g. 5 and 10% w/w) as well as two methods of preparation before the 3D printing process, mortar and pestle and cryogenic milling, were evaluated. The amorphous state of PP was obtained by using cryogenic milling and it was maintained after printing. Two designs were printed by PEBP, a ring and a disk, to evaluate their impact on the release profile of PP. During the in vitro dissolution tests, the implant design, the amount of PP, as well as the crystalline or amorphous state of PP have shown to influence the drug release profile. During the successive steps of preparation of the long-acting implants, blends and raw materials were characterized by DSC and XRD.
在本研究中，基于压力挤出的打印技术（PEBP）的多功能性被用作3D打印工艺，以制造长效可植入剂型。根据药物浓度、制备方式和最终植入物的设计，实现了不同的释放曲线。聚己内酯（PCL）被用作聚合物来维持负载药物的释放。棕榈酸帕利哌酮（PP），一种用于治疗精神分裂症的BCS II类药物，被用作模型药物。评估了两种PP浓度（如5%和10% w/w）以及3D打印工艺前的两种制备方法，即研钵研磨和低温研磨。通过低温研磨获得了PP的无定形态，并在打印后得以保持。通过PEBP打印了两种设计，即环形和盘形，以评估它们对PP释放曲线的影响。在体外溶出试验中，植入物设计、PP的量以及PP的结晶或无定形态均已表明会影响药物释放曲线。在长效植入物的连续制备步骤中，通过差示扫描量热法（DSC）和X射线衍射法（XRD）对混合物和原材料进行了表征。
