Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Düsseldorf, Germany; Department of Pharmaceutical Technologies, Merck KGaA, Darmstadt, Germany.
Department of Pharmaceutical Technologies, Merck KGaA, Darmstadt, Germany.
Int J Pharm. 2021 Mar 15;597:120216. doi: 10.1016/j.ijpharm.2021.120216. Epub 2021 Jan 22.
Brittleness is often described as a restricting material property for the processability of filaments via Fused Deposition Modeling. Especially filaments produced from approved pharmaceutical polymers often tend to fracture between feeding gears, the commonly employed feeding mechanism. In order to enhance their mechanical properties, usually extensive formulation development is performed. This study presents a different strategy to enable the printing of brittle filaments without the use of additional excipients by adapting the feeding mechanism to piston feeding. The polymers Soluplus®, Kollidon® VA64 and Eudragit® E PO were used, which have been reported to be brittle. Ketoconazole was used as model compound at 40% drug load and the influence on the mechanical properties was investigated using the three-point flexural test. In order to gain a better understanding of the mechanism affecting brittleness, filaments were analyzed in terms of crystallinity and miscibility of the components using polarized microscopy, differential scanning calorimetry and X-ray diffraction. Printing was performed with the aim to obtain immediate release tablets. The addition of Ketoconazole resulted in filaments even more brittle than placebo filaments. Nevertheless, the adaption of the feeding mechanism enabled the successful manufacturing of uniform tablets from all formulations.
脆性通常被描述为通过熔融沉积建模（Fused Deposition Modeling）来处理长丝的限制材料特性。特别是由经过批准的药物聚合物生产的长丝往往容易在进料齿轮（常用的进料机构）之间断裂。为了提高它们的机械性能，通常需要进行广泛的配方开发。本研究提出了一种不同的策略，通过将进料机制适应活塞进料来实现无需使用额外赋形剂即可打印脆性长丝。使用了被报道为脆性的聚合物 Soluplus®、Kollidon®VA64 和 Eudragit®E PO。将酮康唑以 40%的药物载量用作模型化合物，并使用三点弯曲试验研究其对机械性能的影响。为了更好地理解影响脆性的机制，使用偏光显微镜、差示扫描量热法和 X 射线衍射法分析了长丝的结晶度和成分的混溶性。打印的目的是获得即刻释放片剂。酮康唑的添加导致长丝比安慰剂长丝更加脆弱。然而，进料机制的适应使得能够成功地从所有配方制造出均匀的片剂。
