TY - JOUR
T1 - 3D printed infliximab suppositories for rectal biologic delivery
AU - Awad, Atheer
AU - Goyanes, Alvaro
AU - Orlu, Mine
AU - Gaisford, Simon
AU - Basit, Abdul W.
N1 - Funding Information:
This project has received funding from the Interreg 2 Seas programme 2014-2020 co-funded by the European Regional Development Fund under subsidy contract “Site Drug 2S07-033”.
Publisher Copyright:
© 2023 The Authors
PY - 2023/3/8
Y1 - 2023/3/8
N2 - Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
AB - Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs.
KW - Biologicals and monoclonal antibodies
KW - Digital medicine production
KW - Extrusion-assisted additve manufacturing of a suppository formulation
KW - Pressure-assisted syringe
KW - Rectal drug delivery
KW - Tumour necrosis factor-alpha (TNF-alpha) inhibitors
KW - Ulcerative colitis (UC) and Crohn's disease (CD)
UR - http://www.scopus.com/inward/record.url?scp=85150863321&partnerID=8YFLogxK
U2 - 10.1016/j.ijpx.2023.100176
DO - 10.1016/j.ijpx.2023.100176
M3 - Article
AN - SCOPUS:85150863321
VL - 5
JO - International Journal of Pharmaceutics: X
JF - International Journal of Pharmaceutics: X
SN - 2590-1567
M1 - 100176
ER -