Division of Advanced Materials and Healthcare Technologies, School of Pharmacy, The University of Nottingham, NG7 2RD, UK.
EPSRC Centre for Innovative Manufacturing in Additive Manufacturing, School of Engineering, UK.
J Control Release. 2017 Sep 10;261:207-215. doi: 10.1016/j.jconrel.2017.06.025. Epub 2017 Jun 28.
A hot melt 3D inkjet printing method with the potential to manufacture formulations in complex and adaptable geometries for the controlled loading and release of medicines is presented. This first use of a precisely controlled solvent free inkjet printing to produce drug loaded solid dosage forms is demonstrated using a naturally derived FDA approved material (beeswax) as the drug carrier and fenofibrate as the drug. Tablets with bespoke geometries (honeycomb architecture) were fabricated. The honeycomb architecture was modified by control of the honeycomb cell size, and hence surface area to enable control of drug release profiles without the need to alter the formulation. Analysis of the formed tablets showed the drug to be evenly distributed within the beeswax at the bulk scale with evidence of some localization at the micron scale. An analytical model utilizing a Fickian description of diffusion was developed to allow the prediction of drug release. A comparison of experimental and predicted drug release data revealed that in addition to surface area, other factors such as the cell diameter in the case of the honeycomb geometry and material wettability must be considered in practical dosage form design. This information when combined with the range of achievable geometries could allow the bespoke production of optimized personalised medicines for a variety of delivery vehicles in addition to tablets, such as medical devices for example.
本文提出了一种热熔 3D 喷墨打印方法，该方法具有在复杂和可适应的几何形状中制造制剂的潜力，可用于控制药物的负载和释放。这是首次使用精确控制的无溶剂喷墨打印生产载药固体制剂，使用天然衍生的 FDA 批准材料（蜂蜡）作为药物载体和非诺贝特作为药物。制备了具有定制几何形状（蜂窝结构）的片剂。通过控制蜂窝单元尺寸，即表面积来对蜂窝结构进行修饰，从而可以控制药物释放曲线，而无需改变制剂。对形成的片剂进行分析表明，药物在块状尺度上均匀分布在蜂蜡中，在微米尺度上存在一些定位的证据。开发了利用扩散的菲克描述的分析模型来允许预测药物释放。将实验和预测的药物释放数据进行比较表明，除了表面积之外，在实际剂型设计中，还必须考虑其他因素，例如蜂窝结构的情况下的单元直径以及材料润湿性。将这些信息与可实现的几何形状范围相结合，可以为各种输送载体（例如医疗设备）的优化个性化药物的定制生产提供便利，而不仅仅是片剂。
