3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets
3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets
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DOI：
10.1016/j.ejpb.2014.12.003
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发表时间：
2015-01-01
影响因子：
4.9
通讯作者：
Basit, Abdul W.
中科院分区：
文献类型：
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作者：
Goyanes, Alvaro;Buanz, Asma B. M.;Basit, Abdul W.
本研究的目的是探索熔融沉积三维打印（FDM 3DP）生产调释药物片剂的潜力。选择用于治疗炎症性肠病（IBD）的两种氨基水杨酸异构体5-氨基水杨酸（5-阿萨，美沙拉嗪）和4-氨基水杨酸（4-阿萨）作为模型药物。商业生产的聚乙烯醇（PVA）长丝在乙醇药物溶液中装载有药物。5-阿萨和4-阿萨链的最终载药量分别为0.06%w/w和0.25%w/w。10.5随后使用FDM 3D打印机打印PVA/4-阿萨和PVA/5-阿萨两者的直径为1.5mm的片剂，并且通过在打印机软件中选择填充百分比来实现改变打印片剂的重量和密度。这些片剂具有很强的机械强度，FDM 3D打印被证明是生产药物5-阿萨的有效工艺。然而，在打印过程中发生了活性4-阿萨的显著热降解（50%），这表明当在超过降解点的高温下打印时，该方法可能不适合于药物。对配制的混合物进行的差示扫描量热法（DSC）和热重分析（TGA）证实了这些发现，同时强调了热分析技术在预测3D打印过程中药物降解问题方面的潜力。在改良Hank碳酸氢盐缓冲液中进行的溶出试验结果表明，两种药物的释放曲线均取决于药物本身和片剂的填充百分比。我们的工作证明了FDM 3DP作为一种高效、低成本的替代方法的潜在作用，可用于生产个性化定制的口服药物剂量，也可用于生产缓释制剂。(C)2014爱思唯尔有限公司版权所有。
The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5 mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. (C) 2014 Elsevier B.V. All rights reserved.