Abstract

Drug release from long-acting intravitreal implants is governed by the coupled effects of diffusion, hydrolysis-driven erosion, and progressive shrinkage of the polymeric matrix. To capture these mechanisms, we solve the diffusion equation in a cylindrical domain whose radius decreases according to the hydrolytic degradation kinetics of PLGA, which follow a pseudo-first-order behaviour in aqueous excess. The resulting formulation combines a modal Bessel expansion with an erosion-controlled time transformation, allowing the evolving geometry and the attenuation of the diffusion modes to be incorporated in a fully mechanistic manner. Within this framework, the shrinkage parameter p quantifies the rate of erosion-induced geometric evolution and enables an accurate reconstruction of the experimental dexamethasone release profile. The solution reproduces both the initial fast-release phase and the extended depletion tail from which the characteristic times t0.50=264.3h and t0.90=996.5h are extracted, providing compact and physically meaningful indicators of the transition between early and late kinetic regimes. Overall, the approach offers a robust and interpretable description of drug release from shrinking polymeric systems and is directly applicable to the design of long-acting intravitreal therapies.

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