Drug-Device Interface Engineering

Abstract

The drug-device interface -- the physical, chemical, and biological boundary where a pharmaceutical agent contacts and interacts with the materials comprising its delivery device -- is the critical engineering zone that determines combination product performance, safety, and regulatory acceptability. Interface phenomena including drug adsorption to device surfaces, leachable extraction from polymer components into drug formulations, chemical degradation catalysed by metal oxides, and protein denaturation at hydrophobic surfaces can reduce drug potency, generate toxic degradants, and compromise device mechanical integrity in ways that neither drug development nor device engineering disciplines independently anticipate. This study presents the Drug-Device Interface Engineering Assessment Framework (DDIEAF), evaluating five interface engineering strategies -- inert passivation surface treatment, drug-compatible polymer selection with extractables modelling, functional surface immobilisation for controlled presentation, nanostructured interface architectures with gradient release, and AI-guided interface design with molecular dynamics validation -- across four drug-device interface contexts: protein biologics in prefilled injectors, small molecule drugs in implantable reservoir systems, nucleic acid therapeutics in microfluidic cartridges, and cytotoxic agents in drug-eluting vascular devices. Our Interface Engineering Performance Score (IEPS) integrates drug stability preservation, leachable control, surface-drug compatibility, release profile fidelity, and biocompatibility maintenance. AI-guided interface design with molecular dynamics validation achieved the highest IEPS (0.924) through computational prediction of drug-surface interaction energies that identified optimal surface chemistries achieving 96% drug recovery from device surfaces, while inert passivation achieved the highest regulatory compliance (0.952) through the most extensively characterised surface treatment methodology with established extractables/leachables profiles