Fratini Costanza, Moroni Sofia, Angelis Davide De, Tiboni Mattia, Balducci Anna Giulia, Rossi Alessandra, Aluigi Annalisa, Amadei Francesco, Casettari Luca
University of Urbino Carlo Bo, Department of Biomolecular Sciences, School of Pharmacy, Via Ca le Suore 2, 61029 Urbino (PU), Italy.
Chiesi Farmaceutici Spa, Preclinical, A&EF Department, Largo Belloli 11/A, 43122 Parma, Italy.
Int J Pharm. 2025 Apr 30;675:125542. doi: 10.1016/j.ijpharm.2025.125542. Epub 2025 Apr 5.
3D printing (3DP) plays a crucial role in accelerating formulation processes and significantly reduces the time needed to transition from concept to prototype. This technology is particularly valuable as it allows researchers to quickly adjust the structure and composition of dosage forms and efficiently evaluate multiple formulations for safety and efficacy. The following research explores the feasibility of using the direct powder extrusion (DPE) technique to produce 3D-printed mini tablets for eventual in vivo preclinical trials in rodents. The DPE method streamlines the manufacturing process into a single step and addresses the limitations commonly associated with Fused Deposition Modeling (FDM). It offers advantages such as customized small-batch production, optimized costs, and minimal waste. This allows pharmaceutical companies to quickly respond to market demands and improve overall product quality through detailed characterization. In this study cellulose-based polymers like Hydroxypropyl Cellulose (HPC-L) and Hydroxypropyl Methylcellulose (HPMC-15LV) were selected as the main matrix excipients, incorporating 10 % w/w of a model drug. The formulations were further optimized to achieve the best flowability and extrudability, as well as the most desirable printing resolution, to produce 3D-printed mini tablets resembling size 9 capsules. Based on the inner diameter of the cannula used for oral administration in rats, tablets measuring 8.6 × 1.8 × 1.8 mm were successfully printed. Thermal analysis (DSC and TGA) and solid-state characterization (FTIR, XRD) were employed to evaluate the physical properties of the powder blends and final 3D-printed products along with the assessment of desirable mechanical features. The successful production of small batches of model 3D-printed mini tablets that are suitable for in vivo testing and present comparable release profiles with conventional employed capsules demonstrated the possibility to implement DPE during preclinical development of novel formulations working independently from suppliers.
3D打印（3DP）在加速制剂工艺过程中发挥着关键作用，并显著减少了从概念到原型过渡所需的时间。这项技术特别有价值，因为它使研究人员能够快速调整剂型的结构和组成，并有效地评估多种制剂的安全性和有效性。以下研究探讨了使用直接粉末挤出（DPE）技术生产3D打印微型片剂以用于最终在啮齿动物体内进行临床前试验的可行性。DPE方法将制造过程简化为一个步骤，并解决了通常与熔融沉积建模（FDM）相关的局限性。它具有定制小批量生产、优化成本和最小浪费等优点。这使制药公司能够快速响应市场需求，并通过详细表征提高整体产品质量。在本研究中，选择了基于纤维素的聚合物，如羟丙基纤维素（HPC-L）和羟丙基甲基纤维素（HPMC-15LV）作为主要的基质辅料，并加入10% w/w的模型药物。对制剂进行了进一步优化，以实现最佳的流动性和可挤出性，以及最理想的打印分辨率，从而生产出类似9号胶囊大小的3D打印微型片剂。根据用于大鼠口服给药的套管内径，成功打印出尺寸为8.6×1.8×1.8 mm的片剂。采用热分析（DSC和TGA）和固态表征（FTIR、XRD）来评估粉末混合物和最终3D打印产品的物理性质，同时评估所需的机械性能。成功生产出适合体内测试且具有与传统胶囊相当释放曲线的小批量3D打印微型片剂模型，证明了在新型制剂临床前开发过程中独立于供应商实施DPE的可能性。
