3D printing of extended-release tablets of theophylline using hydroxypropyl methylcellulose (HPMC) hydrogels
3D printing of extended-release tablets of theophylline using hydroxypropyl methylcellulose (HPMC) hydrogels
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DOI：
10.1016/j.ijpharm.2020.119983
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发表时间：
2020-12-15
影响因子：
5.8
通讯作者：
Shi, Xiaolei
中科院分区：
文献类型：
--
作者：
Cheng, Yiliang;Qin, Hantang;Shi, Xiaolei
使用基于挤出的3D打印机在环境温度下制备具有不同载药量（75、100、125 mg）的半固体片剂。将活性药物成分茶碱上载到由羟丙基甲基纤维素（HPMC）K4 M或E4 M制备的水凝胶中。将HPMC浓度调节至不同水平（10和12%w/w）以满足3D打印的要求。流变学和质地性质，以及释放曲线，显着影响的类型和浓度的赋形剂，无论茶碱剂量使用。打印材料应表现出剪切稀化行为，保持屈服应力小于4000 Pa，损耗因子（tans = G“/G”）在0.2和0.7之间，特别是对于使用当前平台的3D打印目的。SEM图像表明，水凝胶基质表现出多孔结构，其具有将茶碱簇包封在其微观结构内的潜力。体外溶出试验表明，所有片剂的释放延长超过12 h，药物释放动力学模型的计算显示，3D打印的HPMC基质通过扩散和侵蚀机制释放茶碱。赋形剂HPMC K4 M 12%w/w水凝胶是最佳的，以加载茶碱与灵活的剂量组合，由于大的可挤出性和形状保持能力。本研究对流变学性质进行了探索，结果表明，这是一种可行的方法来预测药物释放系统的水凝胶-API共混材料的SSE 3D打印适性和质量。
An extrusion based 3D printer was used to prepare the semi-solid tablets with different drug loading dosages (75, 100, 125 mg) under ambient temperature. The active pharmaceutical ingredient, theophylline, was uploaded within the hydrogels prepared of hydroxypropyl methylcellulose (HPMC) K4M or E4M. The HPMC concentrations were adjusted to different levels (10 and 12% w/w) to fulfill the requirements for 3D printing. Rheological and textural properties, as well as release profiles, were significantly affected by the type and concentration of excipient regardless of theophylline doses used. The printing material should exhibit shear-thinning behavior, keeping yield stress less than 4000 Pa and a loss factor (tans = G ''/G') between 0.2 and 0.7, especially for 3D printing purposes using the current platform. The SEM images demonstrated that the hydrogel matrix exhibited a porous structure, which had the potential to encapsulate the theophylline clusters within its microstructure. The in vitro dissolution test showed that the release of all tablets was extended over 12 h, and the calculation of drug release kinetic models revealed that the 3D printed HPMC matrices release the theophylline by diffusion and erosion mechanisms. The excipient HPMC K4M 12% w/w hydrogel was optimal to load the theophylline with flexible dosage combinations due to the great extrudability and shape retention ability. The exploration of rheological properties was investigated in this study, and the results revealed that it is a feasible method to predict the SSE 3D printability and quality of hydrogel-API blend materials for the drug delivery system.