Exploring tablet design options for tailoring drug release and dose via fused deposition modeling (FDM) 3D printing
Exploring tablet design options for tailoring drug release and dose via fused deposition modeling (FDM) 3D printing
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DOI：
10.1016/j.ijpharm.2020.119987
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发表时间：
2020-12-15
影响因子：
5.8
通讯作者：
Dave, Rajesh N.
中科院分区：
文献类型：
--
作者：
Buyukgoz, Guluzar Gorkem;Soffer, David;Dave, Rajesh N.
本文的目的是探索 FDM 3D 打印的片剂设计方案，以同时调整药物释放和剂量。选择药物、灰黄霉素 (GF)、聚合物、羟丙基纤维素 (HPC) 和加工温度，以避免药物与聚合物相互作用产生的混杂效应。使用双螺杆挤出机制备含有 0-30 wt% GF 的长丝。使用固定或变化的药物浓度细丝、固定或变化的片剂尺寸、或安慰剂和药物丰富区域的组合打印五种片剂设计。五个选项中有两个达到了主要目标；用于固定片剂尺寸的不同药物浓度丝或打印具有不同尺寸的内部安慰剂区域的固定尺寸双片剂。药物溶出曲线分析表明，片剂表面积与体积 (SA/V) 之比是主要因素，较高的 SA/V 比导致较快的释放速率，主要与药物量或其在片剂中的位置无关。在大多数情况下，HPC 的使用导致接近零阶的释放。对于双片剂，观察到与安慰剂壳厚度成比例的长滞后时间。这些结果表明，除了改变片剂尺寸之外，还需要其他设计方案来实现基于 FDM 的 3D 打印个性化剂量所需的药物释放。
The aim of this paper was to explore tablet design options for FDM 3D printing for simultaneous tailoring of drug release and dose. The drug, griseofulvin (GF), the polymer, hydroxypropyl cellulose (HPC), and processing temperatures were selected to avoid confounding effects arising from drug-polymer interactions. Filaments containing 0-30 wt% GF were prepared using a twin-screw extruder. Five tablet designs were printed using combinations of fixed or varying drug-concentration filaments, fixed or varying tablet sizes, or placebo and drug-rich regions. Two of five options met the main objective; varying drug-concentration filaments for fixed tablet size or printing fixed size duo-tablet having internal placebo regions of varying sizes. Analysis of the drug dissolution profiles revealed that the tablet surface area to volume (SA/V) ratio was the dominant factor, a higher SA/V ratio resulted in a faster release rate, mostly independent of the drug amount or its placement within the tablet. Use of HPC led to near zero-order release for most cases. For duo-tablets, long lag times proportional to placebo shell-thickness were observed. These results suggest that design options other than varying the tablet size would be needed to achieve desired drug release from FDM-based 3D printed personalized dosages.