Material extrusionbased additive manufacturing (ME-AM) has been recently adopted by the pharmaceutical field as a potential method for decentralised small-batch manufacturing of personalised solid dosage forms. The unique advantage of ME-AM is the ability to implement a wide range of micro-scale internal structures within a dosage form that can be used to manipulate the drug release kinetics. However, currently, there is no fundamental understanding of how the design of microstructures of a dosage form can control drug release. This study used polycaprolactone/ibuprofen as the model system to investigate four key geometric parameters of microstructures, printing pore length (by changing layer number), porosity (by varying the pore width), pore shape (by changing the filament intersection angles from 90° to 30°), and pore alignment, which allowed the construction of a wide range of interior microstructures within a drug-loaded 3D construct. This is the first work to have systematically investigated the interrelated effects of these parameters. The surface area/volume ratio (SA/V) of the constructs were simulated using the newly developed VOLume COnserving model (VOLCO). Four key points were found from this study: (1) drug release rate significantly increased with increasing porosity; (2) pore shape (or filament intersection angles) showed no significant effect on the drug release rate; (3) for the first time, a critical layer number (Lc) or (pore length) effect was observed and reported. The layer number only had a significant impact on drug release when below Lc; (4) when pore width was small, pore alignment significantly affected the release kinetics. The outcomes of this study provide clear principles and design guidance on using microstructures to control drug release from ME-AM solid dosage forms.

基于材料挤出的增材制造 (ME-AM) 最近已被制药领域用作分散小批量个性化固体剂型制造的潜在方法。ME-AM 的独特优势是能够在一个剂型中实现各种微尺度内部结构，可用于操纵药物释放动力学。然而，目前对剂型的微观结构设计如何控制药物释放还没有基本的了解。本研究使用聚己内酯/布洛芬作为模型系统研究微观结构的四个关键几何参数，印刷孔长度（通过改变层数）、孔隙率（通过改变孔宽度）、孔形状（通过改变细丝交叉角度从 90°到 30°），和孔排列，这允许在载药 3D 结构中构建各种内部微结构。这是系统地研究这些参数的相关影响的第一项工作。表面积/体积比（SA/V ) 使用新开发的 VOLume COnserving 模型 (VOLCO) 进行模拟。本研究发现四个关键点：（1）随着孔隙率的增加，药物释放速率显着增加；(2)孔隙形状(或细丝交叉角)对药物释放速率无显着影响；(3) 首次观察并报告了临界层数 ( Lc ) 或（孔长）效应。层数仅在低于Lc时对药物释放有显着影响；(4) 当孔宽较小时，孔排列对释放动力学有显着影响。这项研究的结果为使用微结构控制 ME-AM 固体剂型的药物释放提供了明确的原则和设计指导。