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 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.
Int J Pharm. 2022 Apr 25;618:121662. doi: 10.1016/j.ijpharm.2022.121662. Epub 2022 Mar 12.
In this work, two technologies were used to prepare long-acting implantable dosage forms in the treatment of schizophrenia. Hot-melt extrusion (HME) as well as fused deposition modelling (FDM) were used concomitantly to create personalized 3D printed implants. Different formulations were prepared using an amorphous PLA as matrix polymer and different solid-state plasticizers. Paliperidone palmitate (PP), a heat sensitive drug prescribed in the treatment of schizophrenia was chosen as model drug. After extrusion, different formulations were characterized using DSC and XRD. Then, an in vitro dissolution test was carried out to discriminate the formulation allowing a sustained drug release of PP. The formulation showing a sustained drug release of the drug was 3D printed as an implantable dosage form. By modulating the infill, the release profile was related to the proper design of tailored dosage form and not solely to the solubility of the drug. Indeed, different release profiles were achieved over 90 days using only one formulation. In addition, a stability test was performed on the 3D printed implants for 3 months. The results showed the stability of the amorphous state of PP, independently of the temperature as well as the integrity of the matrix and the drug.
在这项工作中，使用了两种技术来制备长效可植入剂型，用于治疗精神分裂症。热熔挤出（HME）和熔融沉积建模（FDM）同时用于创建个性化的 3D 打印植入物。使用无定形 PLA 作为基质聚合物和不同的固态增塑剂制备了不同的配方。棕榈酸帕利哌酮（PP）是一种热敏药物，用于治疗精神分裂症，被选为模型药物。挤出后，使用 DSC 和 XRD 对不同配方进行了表征。然后，进行了体外溶出试验，以区分允许 PP 持续释放的配方。显示药物持续释放的配方被 3D 打印为可植入剂型。通过调节填充，释放曲线与定制剂型的适当设计有关，而不仅仅与药物的溶解度有关。事实上，仅使用一种配方即可在 90 天内实现不同的释放曲线。此外，对 3D 打印植入物进行了 3 个月的稳定性测试。结果表明，PP 的无定形状态稳定，独立于温度以及基质和药物的完整性。
