Seoane-Viaño Iria, Ong Jun Jie, Luzardo-Álvarez Asteria, González-Barcia Miguel, Basit Abdul W, Otero-Espinar Francisco J, Goyanes Alvaro
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela, Santiago de Compostela 15782, Spain.
Department of Pharmaceutics, UCL School of Pharmacy, University College London, London WC1N 1AX, UK.
Asian J Pharm Sci. 2021 Jan;16(1):110-119. doi: 10.1016/j.ajps.2020.06.003. Epub 2020 Jul 9.
Ulcerative colitis is a global health problem, affecting millions of individuals worldwide. As an inflammatory condition localised in the large intestine, rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects. Here, for the first time, self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion (SSE) 3D printer. The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients (Gelucire 44/14 or Gelucire 48/16) and coconut oil. Although both suppository formulations had the appropriate viscosity characteristics for printing, the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system. The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories. Although the tacrolimus release profiles were significantly different, both suppository systems released more than 80% drug within 120 min. DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories. In summary, this article reports on the fabrication of 3D printed self-supporting suppositories to deliver personalised doses of a narrow therapeutic index drug, with potential benefits for patients with ulcerative colitis.
溃疡性结肠炎是一个全球性的健康问题，影响着全球数百万人。作为一种局限于大肠的炎症性疾病，直肠给药免疫抑制疗法（如他克莫司）是一种很有前景的策略，可在将全身副作用降至最低的同时，使药物在作用部位的浓度最大化。在此，首次使用药物半固体挤出（SSE）3D打印机，在无需模具的情况下制备了自支撑3D打印他克莫司栓剂。使用两种脂质药物辅料（Gelucire 44/14或Gelucire 48/16）和椰子油的组合，将栓剂垂直打印成三种不同尺寸。尽管两种栓剂配方都具有适合打印的粘度特性，但与Gel 48系统相比，Gel 44配方在挤出时所需的能量和力更少。Gel 44栓剂崩解更快，但他克莫司释放比Gel 48栓剂更慢。尽管他克莫司的释放曲线有显著差异，但两种栓剂系统在120分钟内均释放了超过80%的药物。DSC和XRD分析在确定栓剂中药物的固态性质方面尚无定论。总之，本文报道了3D打印自支撑栓剂的制备，以递送窄治疗指数药物的个性化剂量，对溃疡性结肠炎患者可能有益。
