A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants

He, Yinfeng; Foralosso, Ruggero; Ferraz Trindade, Gustavo; Ilchev, Alexander; Cantu, Laura Ruiz; Clark, Elizabeth; Khaled, Shaban; Hague, Richard J M; Tuck, Christopher J; Rose, Felicity R A J; Mantovani, Giuseppe; Irvine, Derek; Roberts, Clive J; Wildman, Ricky D

Abstract

We propose a strategy for creating tuneable 3D printed drug delivery devices. 3D printing offers the opportunity for improved compliance and patient treatment outcomes through personalisation, but bottlenecks include finding formulations that provide a choice of drug loading and release rate, are tuneable and avoid the need for surgical removal. Our solution is to exploit 3D inkjet printing freedoms. We use a reactive prodrug that can polymerize into drug-attached macromolecules during 3D printing, and by tuning the hydrophilicity we can facilitate or hinder hydrolysis, which in turn controls the drug release. To demonstrate this approach, we attach ibuprofen to 2-hydroxyethyl acrylate through a cleavable ester bond, formulate it for inkjet 3D printing, and then print to produce a solid dosage form. This allows a much higher loading than is usually achievable-in our case up to 58 wt%. Of equal importance, the 3D inkjet printing freedoms mean that our drug delivery device is highly tuneable: by selection of spacer monomers to adjust the hydrophilicity; through geometry; by spatially varying the components. Consequently, we create bespoke, hierarchical release systems, from the molecular to macro. This approach represents a new paradigm for the formulation of printable inks for drug-loaded medical devices.

Citation

He, Y., Foralosso, R., Ferraz Trindade, G., Ilchev, A., Cantu, L. R., Clark, E., Khaled, S., Hague, R. J. M., Tuck, C. J., Rose, F. R. A. J., Mantovani, G., Irvine, D., Roberts, C. J., & Wildman, R. D. (2020). A Reactive Prodrug Ink Formulation Strategy for Inkjet 3D Printing of Controlled Release Dosage Forms and Implants. Advanced Therapeutics, 3(6), Article 1900187. https://doi.org/10.1002/adtp.201900187

• Journal Article Type: Article
• Acceptance Date: Dec 18, 2019
• Online Publication Date: Feb 19, 2020
• Publication Date: 2020-06
• Deposit Date: Feb 9, 2020
• Publicly Available Date: Feb 20, 2021
• Journal: Advanced Therapeutics
• Electronic ISSN: 2366-3987
• Publisher: Wiley-VCH Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 6
• Article Number: 1900187
• DOI: https://doi.org/10.1002/adtp.201900187
• Keywords: Additive Manufacturing; Inkjet; Pro-drug; Controlled release
• Public URL: https://nottingham-repository.worktribe.com/output/3933263
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/adtp.201900187