School of Pharmacy, University of East Anglia, Norwich, UK.
School of Chemistry, University of East Anglia, Norwich, UK.
Eur J Pharm Biopharm. 2022 Aug;177:113-125. doi: 10.1016/j.ejpb.2022.06.013. Epub 2022 Jun 29.
A range of 3D printing methods have been investigated intensively in the literature for manufacturing personalised solid dosage forms, with infill density commonly used to control release rates. However, there is limited mechanistic understanding of the impacts of infill adjustments on in vitro performance when printing tablets of constant dose. In this study, the effects and interplay of infill pattern and tablet geometry scaling on dose and drug release performance were investigated. Paracetamol (PAC) was used as a model drug. An immediate release erodible system (Eudragit E PO) and an erodible swellable system (Soluplus) were prepared via wet granulation into granules and printed using Arburg Plastic Freeforming (APF). Both binary formulations, despite not FDM printable, were successfully APF printed and exhibited good reproducibility compared to pharmacopoeia specification. The physical form of the drug and its integrity following granulation and printing was assessed using DSC, PXRD and ATR-FTIR. Two infill patterns (SM1 and SM2) were employed to print tablets with equal porosity, but different pore size, structure and surface area to volume ratio (SA/V). Geometry scaling (tablet height and diameter) of Eudragit-PAC tablets was not found to significantly influence the release rate of the tablets with 30 to 70% infill density. When increased to 90% infill density, geometric scaling was found to have a significant effect on release rate with the constant diameter tablet releasing faster than the constant height tablet. Soluplus-PAC tablets printed using different infill patterns demonstrated similar release profiles, due to swelling. Geometric parameters were found to significantly influence release profiles for tablets printed at certain infill densities giving new insight into how software parameters can be used to tune drug release.
已有大量的 3D 打印技术被广泛应用于个体化固体制剂的制造中，其中填充密度通常被用来控制释放速率。然而，当打印等剂量的片剂时，对于填充调整对体外性能的影响，我们的机械理解还很有限。在这项研究中，我们研究了填充图案和片剂几何形状缩放对剂量和药物释放性能的影响及其相互作用。扑热息痛（PAC）被用作模型药物。采用湿法制粒法将速释可蚀蚀系统（Eudragit E PO）和可蚀溶胀系统（Soluplus）制成颗粒，并采用 Arburg Plastic Freeforming（APF）进行打印。尽管这两种配方都不能进行 FDM 打印，但它们都可以通过 APF 成功打印，并且与药典规范相比表现出良好的重现性。采用 DSC、PXRD 和 ATR-FTIR 评估了药物的物理形态及其在制粒和打印后的完整性。采用两种填充图案（SM1 和 SM2）打印具有相同孔隙率但不同孔径、结构和表面积体积比（SA/V）的片剂。对于 Eudragit-PAC 片剂，几何形状缩放（片剂高度和直径）并未显著影响填充密度为 30%至 70%的片剂的释放速率。当填充密度增加到 90%时，几何形状缩放对释放速率有显著影响，直径固定的片剂比高度固定的片剂释放速度更快。采用不同填充图案打印的 Soluplus-PAC 片剂由于溶胀而表现出相似的释放曲线。几何参数被发现对在特定填充密度下打印的片剂的释放曲线有显著影响，这为如何使用软件参数来调整药物释放提供了新的见解。
