School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, UK; Faculty of Medical Sciences and Public Health, Anglia Ruskin University, Chelmsford, UK.
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, UK; Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Warsaw, Poland.
Eur J Pharm Sci. 2018 Jun 15;118:191-199. doi: 10.1016/j.ejps.2018.03.019. Epub 2018 Mar 17.
Fused deposition modelling (FDM) 3D printing has shown the most immediate potential for on-demand dose personalisation to suit particular patient's needs. However, FDM 3D printing often involves employing a relatively large molecular weight thermoplastic polymer and results in extended release pattern. It is therefore essential to fast-track drug release from the 3D printed objects. This work employed an innovative design approach of tablets with unique built-in gaps (Gaplets) with the aim of accelerating drug release. The novel tablet design is composed of 9 repeating units (blocks) connected with 3 bridges to allow the generation of 8 gaps. The impact of size of the block, the number of bridges and the spacing between different blocks was investigated. Increasing the inter-block space reduced mechanical resistance of the unit, however, tablets continued to meet pharmacopeial standards for friability. Upon introduction into gastric medium, the 1 mm spaces gaplet broke into mini-structures within 4 min and met the USP criteria of immediate release products (86.7% drug release at 30 min). Real-time ultraviolet (UV) imaging indicated that the cellulosic matrix expanded due to swelling of hydroxypropyl cellulose (HPC) upon introduction to the dissolution medium. This was followed by a steady erosion of the polymeric matrix at a rate of 8 μm/min. The design approach was more efficient than a comparison conventional formulation approach of adding disintegrants to accelerate tablet disintegration and drug release. This work provides a novel example where computer-aided design was instrumental at modifying the performance of solid dosage forms. Such an example may serve as the foundation for a new generation of dosage forms with complicated geometric structures to achieve functionality that is usually achieved by a sophisticated formulation approach.
熔融沉积成型（FDM）3D 打印技术在按需定制剂量以满足特定患者需求方面显示出最直接的潜力。然而，FDM 3D 打印通常涉及使用相对较高分子量的热塑性聚合物，导致释放模式延长。因此，从 3D 打印物体中快速释放药物至关重要。这项工作采用了一种具有独特内置间隙（Gaplets）的片剂的创新设计方法，旨在加速药物释放。这种新型片剂设计由 9 个重复单元（块）组成，通过 3 个桥连接，以产生 8 个间隙。研究了块的大小、桥的数量和不同块之间的间距对药物释放的影响。增加块之间的空间减少了单元的机械阻力，但是片剂仍然符合易碎性的药典标准。当引入胃介质中时，1mm 间隙的 Gaplet 在 4 分钟内分解成微型结构，并符合 USP 即时释放产品的标准（30 分钟时 86.7%的药物释放）。实时紫外（UV）成像表明，羟丙基纤维素（HPC）在引入溶解介质后，纤维素基质因溶胀而膨胀。随后，聚合物基质以 8μm/min 的速度稳定侵蚀。与比较传统的添加崩解剂来加速片剂崩解和药物释放的制剂方法相比，这种设计方法更有效。这项工作提供了一个新的例子，计算机辅助设计在改变固体制剂的性能方面发挥了作用。这样的例子可以作为新一代具有复杂几何结构的剂型的基础，以实现通常通过复杂配方方法实现的功能。
