Food Science and Human Nutrition Department, Iowa State University, Ames, IA 50011, USA.
Industrial and Manufacturing Systems Engineering Department, Iowa State University, Ames, IA 50011, USA.
Int J Pharm. 2020 Dec 15;591:119983. doi: 10.1016/j.ijpharm.2020.119983. Epub 2020 Oct 13.
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 (tanδ = 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.
一种基于挤压的 3D 打印机被用于在环境温度下制备具有不同药物加载剂量（75、100、125mg）的半固体片剂。活性药物成分茶碱被上传到由羟丙基甲基纤维素（HPMC）K4M 或 E4M 制备的水凝胶中。HPMC 浓度被调整到不同水平（10%和 12%w/w）以满足 3D 打印的要求。流变学和质地特性以及释放曲线都受到赋形剂类型和浓度的显著影响，而与使用的茶碱剂量无关。打印材料应表现出剪切稀化行为，使屈服应力小于 4000Pa，损耗因子（tanδ=G''/G'）在 0.2 到 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，水凝胶基质呈现多孔结构，有可能将茶碱簇封装在其微结构内。体外溶解试验表明，所有片剂的释放都延长了 12 小时以上，药物释放动力学模型的计算表明，3D 打印的 HPMC 基质通过扩散和侵蚀机制释放茶碱。由于具有良好的可挤出性和形状保持能力，HPMC K4M 12%w/w 水凝胶赋形剂是负载茶碱的最佳选择，可以实现灵活的剂量组合。本研究探讨了流变性能，结果表明，这是一种预测 SSE 3D 打印性和药物传递系统中水凝胶-API 混合物材料质量的可行方法。
