Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
Int J Pharm. 2020 Dec 15;591:119987. doi: 10.1016/j.ijpharm.2020.119987. Epub 2020 Oct 16.
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.
本文旨在探索 FDM 3D 打印中可用于同时控制药物释放和剂量的片剂设计方案。选择灰黄霉素（GF）作为药物、羟丙纤维素（HPC）作为聚合物以及加工温度，以避免药物-聚合物相互作用产生的混杂影响。使用双螺杆挤出机制备含有 0-30wt%GF 的长丝。使用固定或变化药物浓度长丝、固定或变化片剂尺寸或安慰剂和富药区域的组合打印了五种片剂设计。五个选项中的两个满足了主要目标；固定片剂尺寸的变化药物浓度长丝或打印具有不同尺寸内部安慰剂区域的固定尺寸双片剂。药物溶解曲线的分析表明，片剂表面积与体积（SA/V）比是主要因素，较高的 SA/V 比导致更快的释放速率，主要与药物数量或其在片剂中的位置无关。对于大多数情况，使用 HPC 导致接近零级释放。对于双片剂，观察到与安慰剂壳层厚度成正比的长滞后时间。这些结果表明，需要除了改变片剂尺寸之外的设计方案，才能从基于 FDM 的 3D 打印个性化剂量中实现所需的药物释放。
