Controlled Drug Release from Biodegradable Implants

Abstract

Biodegradable implants fabricated from poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly(ortho esters), and silk fibroin offer programmable drug release lasting weeks to years while eliminating the need for surgical retrieval, yet achieving predictable, reproducible release kinetics from degrading polymer matrices remains a persistent formulation challenge. The interplay between polymer chain scission, crystallinity evolution, pore formation, osmotic pressure, and local pH changes creates complex, non-linear release profiles that deviate substantially from theoretical predictions based on simple diffusion or erosion models. This study presents the Biodegradable Implant Drug Release Assessment Framework (BIDRAF), evaluating five controlled release strategies -- monolithic PLGA matrix diffusion, reservoir-membrane systems with rate-controlling barriers, multi-layered sequential release architectures, stimuli-responsive polymer composites, and computationally optimised formulation design -- across four release performance tasks: release rate consistency, burst effect minimisation, payload utilisation efficiency, and in vitro-in vivo concordance. Our Controlled Release Performance Index (CRPI) integrates rate stability, burst suppression, payload efficiency, IVIVC strength, and manufacturing reproducibility. Computationally optimised formulation design achieved the highest CRPI (0.922) through machine learning models trained on 14,600 dissolution profiles that predicted optimal polymer composition, molecular weight, and fabrication parameters to achieve target release profiles with 92% concordance, while multi-layered architectures achieved the highest burst suppression (0.960) through barrier coatings that reduced initial burst release from 32% to below 5% of total payload