Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption
Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption
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DOI：
10.1016/j.ijpharm.2018.04.010
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发表时间：
2018-06-10
影响因子：
5.8
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
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作者：
Kadry, Hossam;Al-Hilal, Taslim A.;Ahsan, Fakhrul
三维打印（3DP）虽然是为非医疗应用而开发的，一度被认为只是未来派，但最近已被用于医药产品的制造。然而，现有用于打印药物产品的原料（墨水和长丝）存在各种缺点，包括缺乏生物相容性、挤出性和打印适性不足、载药量差和不稳定。在这里，我们试图开发一种使用单一药用聚合物、不含添加剂的长丝，它可以具有多种用途，并通过计算设计进行操作，以制备具有所需释放和吸收模式的片剂。因此，我们使用羟丙基甲基纤维素（HPMC）和模型药物地尔硫卓来制备无药和药物浸渍的细丝，并研究它们的热性能和结晶特性，研究细丝的细胞毒性，设计和打印具有各种填充密度和图案的片剂。通过交替使用不含药物和药物浸渍的细丝，我们制造了各种类型的片剂，研究了药物释放曲线，并评估了大鼠的口服吸收。地尔硫卓和 HPMC 在挤出和打印温度下都很稳定，载药量为 10% (w/w)。填充密度以及填充模式影响药物释放曲线，因此，当填充密度增加到 100% 时，药物释放百分比急剧下降。具有交替的无药层和载药层的片剂表现出延迟和间歇性药物释放，这取决于载药层何时遇到溶出介质。重要的是，口服吸收模式准确地再现了药物释放曲线，并显示了药物从大鼠胃肠道（GIT）的立即、延长、延迟和间歇性吸收。总的来说，我们在这里证明了用于 3D 打印机的细丝可以由不含添加剂的药用聚合物制备，并且新颖的计算设计允许制造能够在口服后产生不同吸收模式的片剂。
Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no additives, and the novel computational design allows for fabricating tablets with the capability of producing distinct absorption patterns after oral administration.