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

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