Awad Atheer, Hollis Eleanor, Goyanes Alvaro, Orlu Mine, Gaisford Simon, Basit Abdul W
Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
FabRx Ltd., Henwood House, Henwood, Ashford, Kent TN24 8DH, UK.
Int J Pharm X. 2023 Jan 29;5:100165. doi: 10.1016/j.ijpx.2023.100165. eCollection 2023 Dec.
Acute severe ulcerative colitis (ASUC) is a growing health burden that often requires treatment with multiple therapeutic agents. As inflammation is localised in the rectum and colon, local drug delivery using suppositories could improve therapeutic outcomes. Three-dimensional (3D) printing is a novel manufacturing tool that permits the combination of multiple drugs in personalised dosage forms, created based on each patient's disease condition. This study, for the first time, demonstrates the feasibility of producing 3D printed suppositories with two anti-inflammatory agents, budesonide and tofacitinib citrate, for the treatment of ASUC. As both drugs are poorly water-soluble, the suppositories' ability to self-emulsify was exploited to improve their performance. The suppositories were fabricated via semi-solid extrusion (SSE) 3D printing and contained tofacitinib citrate and budesonide in varying doses (10 or 5 mg; 4 or 2 mg, respectively). The suppositories displayed similar dissolution and disintegration behaviours irrespective of their drug content, demonstrating the flexibility of the technology. Overall, this study demonstrates the feasibility of using SSE 3D printing to create multi-drug suppositories for the treatment of ASUC, with the possibility of titrating the drug doses based on the disease progression.
急性重症溃疡性结肠炎(ASUC)是一种日益加重的健康负担,通常需要多种治疗药物联合治疗。由于炎症局限于直肠和结肠,使用栓剂进行局部给药可改善治疗效果。三维(3D)打印是一种新型制造工具,能够将多种药物组合成个性化剂型,根据每位患者的病情定制。本研究首次证明了生产含有两种抗炎药物布地奈德和枸橼酸托法替布的3D打印栓剂用于治疗ASUC的可行性。由于两种药物的水溶性都很差,因此利用栓剂的自乳化能力来提高其性能。这些栓剂通过半固体挤出(SSE)3D打印制造,含有不同剂量的枸橼酸托法替布和布地奈德(分别为10或5毫克;4或2毫克)。无论药物含量如何,栓剂都表现出相似的溶解和崩解行为,证明了该技术的灵活性。总体而言,本研究证明了使用SSE 3D打印制造用于治疗ASUC的多药物栓剂的可行性,并有可能根据疾病进展调整药物剂量。