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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

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


Authors

YINFENG HE Yinfeng.He@nottingham.ac.uk
Transitional Assistant Professor

Ruggero Foralosso

Gustavo Ferraz Trindade

Alexander Ilchev

Laura Ruiz Cantu

Elizabeth Clark

Shaban Khaled

RICHARD HAGUE RICHARD.HAGUE@NOTTINGHAM.AC.UK
Professor of Additive Manufacturing

CHRISTOPHER TUCK CHRISTOPHER.TUCK@NOTTINGHAM.AC.UK
Professor of Materials Engineering

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FELICITY ROSE FELICITY.ROSE@NOTTINGHAM.AC.UK
Professor of Biomaterials and Tissue Engineering

DEREK IRVINE derek.irvine@nottingham.ac.uk
Professor of Materials Chemistry

RICKY WILDMAN RICKY.WILDMAN@NOTTINGHAM.AC.UK
Professor of Multiphase Flow and Mechanics



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.

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

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