Prasad Elke, Robertson John, Halbert Gavin W
EPSRC Future Manufacturing Research Hub in Continuous Manufacturing and Advanced Crystallisation, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK.
Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Polymers (Basel). 2024 Sep 11;16(18):2566. doi: 10.3390/polym16182566.
Additive manufacturing of pharmaceutical formulations offers advanced micro-structure control of oral solid dose (OSD) forms targeting not only customised dosing of an active pharmaceutical ingredient (API) but also custom-made drug release profiles. Traditionally, material extrusion 3D printing manufacturing was performed in a two-step manufacturing process via an intermediate feedstock filament. This process was often limited in the material space due to unsuitable (brittle) material properties, which required additional time to develop complex formulations to overcome. The objective of this study was to develop an additive manufacturing MicroFactory process to produce an immediate release (IR) OSD form containing 250 mg of mefenamic acid (MFA) with consistent drug release. In this study, we present a single-step additive manufacturing process employing a novel, filament-free melt extrusion 3D printer, the MicroFactory, to successfully print a previously 'non-printable' brittle Soluplus-based formulation of MFA, resulting in targeted IR dissolution profiles. The physico-chemical properties of 3D printed MFA-Soluplus-D-sorbitol formulation was characterised by thermal analysis, Fourier Transform Infrared spectroscopy (FTIR), and X-ray Diffraction Powder (XRPD) analysis, confirming the crystalline state of mefenamic acid as polymorphic form I. Oscillatory temperature and frequency rheology sweeps were related to the processability of the formulation in the MicroFactory. 3D printed, micro-structure controlled, OSDs showed good uniformity of mass and content and exhibited an IR profile with good consistency. Fitting a mathematical model to the dissolution data correlated rate parameters and release exponents with tablet porosity. This study illustrates how additive manufacturing via melt extrusion using this MicroFactory not only streamlines the manufacturing process (one-step vs. two-step) but also enables the processing of (brittle) pharmaceutical immediate-release polymers/polymer formulations, improving and facilitating targeted in vitro drug dissolution profiles.
药物制剂的增材制造可实现口服固体制剂（OSD）的先进微观结构控制，不仅能针对活性药物成分（API）进行定制给药，还能实现定制的药物释放曲线。传统上，材料挤出3D打印制造是通过中间原料长丝在两步制造过程中进行的。由于材料性能不合适（易碎），该过程在材料空间上往往受到限制，这需要额外的时间来开发复杂的制剂以克服这一问题。本研究的目的是开发一种增材制造微工厂工艺，以生产含有250毫克甲芬那酸（MFA）且药物释放一致的速释（IR）OSD剂型。在本研究中，我们展示了一种单步增材制造工艺，该工艺采用新型无丝熔融挤出3D打印机——微工厂，成功打印出先前“不可打印”的基于Soluplus的易碎MFA制剂，从而实现了目标IR溶出曲线。通过热分析、傅里叶变换红外光谱（FTIR）和X射线衍射粉末（XRPD）分析对3D打印的MFA-Soluplus-D-山梨醇制剂的物理化学性质进行了表征，证实甲芬那酸的结晶状态为I型多晶型。振荡温度和频率流变扫描与制剂在微工厂中的加工性能相关。3D打印的、微观结构可控的OSD显示出良好的质量和含量均匀性，并呈现出具有良好一致性的IR曲线。将数学模型拟合到溶出数据中，将速率参数和释放指数与片剂孔隙率相关联。本研究说明了使用这种微工厂通过熔融挤出进行增材制造不仅简化了制造过程（一步法与两步法），还能够加工（易碎的）药物速释聚合物/聚合物制剂，改善并促进了目标体外药物溶出曲线。
