College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Int J Pharm. 2021 May 1;600:120524. doi: 10.1016/j.ijpharm.2021.120524. Epub 2021 Mar 26.
Some of the major issues with the development of FDM 3D printed tablets are slow drug release, lack of drug-polymer miscibility, high processing temperature, and poor printability. In this investigation, these issues were addressed by using a novel physicochemical principle called acid-base supersolubilization (ABS) previously developed in our laboratory. The aqueous solubility of a basic drug, haloperidol, was increased to ~300 mg/g of solution by adding glutaric acid, and, upon drying, the concentrated solutions produced amorphous materials. Similar amorphous systems could also be produced by heating haloperidol-glutaric acid mixtures. Filaments for 3D printing were prepared by melt extrusion of formulations containing 15% w/w haloperidol and 10.5% glutaric acid (1:2 M ratio) along with 74.5% polymers, such as Kollidon® VA64 alone or its mixtures with Affinisol™ 15cP. Filaments could be extruded and printed at low temperatures of 115 and 120 °C, respectively. Haloperidol was fully miscible in the formulations because of the acid-base interaction and formed amorphous systems even at higher drug loads. Although filaments of haloperidol-Kollidon® VA64 mixtures by themselves cannot be printed, the printability of formulation improved such that those containing glutaric acid were printable. Drug release rates from the formulations at pH 2 and 6.8 were rapid and complete.
FDM 3D 打印片剂发展存在一些主要问题，包括药物释放缓慢、缺乏药物-聚合物混溶性、加工温度高和可印刷性差。在这项研究中，我们使用了一种新的物理化学原理——酸碱超增溶（ABS）来解决这些问题，该原理是我们实验室之前开发的。碱性药物氟哌啶醇的水溶解度通过添加戊二酸增加到约 300mg/g 的溶液，干燥后，浓缩溶液产生无定形物质。通过加热氟哌啶醇-戊二酸混合物也可以产生类似的无定形系统。用于 3D 打印的长丝是通过挤出含有 15%w/w 氟哌啶醇和 10.5%戊二酸（1:2 M 比）以及 74.5%聚合物（如 Kollidon® VA64 单独或与 Affinisol™ 15cP 的混合物）的制剂来制备的。长丝可以在 115 和 120°C 的低温下挤出和打印。由于酸碱相互作用，氟哌啶醇在制剂中完全混溶，即使在较高的药物负载下也形成无定形系统。尽管氟哌啶醇-Kollidon® VA64 混合物本身的长丝不能打印，但制剂的可印刷性得到了改善，以至于含有戊二酸的制剂可以打印。在 pH 2 和 6.8 时，制剂的药物释放速率很快且完全。
