Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets
Tablet fragmentation without a disintegrant: A novel design approach for accelerating disintegration and drug release from 3D printed cellulosic tablets
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DOI：
10.1016/j.ejps.2018.03.019
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发表时间：
2018-06-15
影响因子：
4.6
通讯作者：
Alhnan, Mohamed A.
中科院分区：
文献类型：
--
作者：
Arafat, Basel;Wojsz, Magdalena;Alhnan, Mohamed A.
熔融沉积成型（FDM）3D打印显示出最直接的按需剂量个性化潜力，以满足特定患者的需求。然而，FDM 3D打印通常涉及使用相对大分子量的热塑性聚合物，并导致延长释放图案。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创新的设计方法，片剂具有独特的内置间隙（Gaplets），目的是加速药物释放。新的片剂设计由9个重复单元（嵌段）组成，其与3个桥连接以允许产生8个间隙。研究了块体尺寸、桥的数量和不同块体之间的间距的影响。增加块间空间降低了装置的机械阻力，然而，片剂继续符合药典的脆碎度标准。在引入胃介质后，Imm空间的间隙片在4分钟内破裂成微型结构，并且达到立即释放产品的USP标准（在30分钟时86.7%的药物释放）。实时紫外（UV）成像表明，由于羟丙基纤维素（HPC）引入溶出介质后溶胀，纤维素基质膨胀。这是其次是一个稳定的侵蚀的聚合物基质的速率为8 μ m/min。的设计方法是更有效的比比较传统的配方方法加入崩解剂，以加速片剂崩解和药物释放。这项工作提供了一个新的例子，其中计算机辅助设计是工具的修改性能的固体剂型。这样的实例可以作为具有复杂几何结构的新一代剂型的基础，以实现通常通过复杂的配制方法实现的功能。
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 ma 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 a a rate of 8 mu m/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 a 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.