Dynamics of Interfacial Diffusion Control in Amphiphilic Lipid-Coated Micro-Particles for Stochastic Release Systems

Abstract

The release of hydrophilic solutes from micron scale particulate formulations can be understood as an interfacial transport problem in which diffusion across a heterogeneous amphiphilic coating competes with dissolution and convective removal in the surrounding medium. Here we reinterpret a glycerin fatty acid ester (GFAE) coated thiamine (vitamin B1) micro particle formulation as a condensed matter system: a soft matter core shell geometry whose effective permeability is set by the nanoscale organization of amphiphilic lipids at the interface. Using in vivo time course serum measurements in mice as a proxy for a stochastic sink, we compare the coated formulation (UTEV) with a composition matched uncoated comparator (UMFG). Early time systemic appearance is similar, whereas late time levels are enhanced for the coated particles, implying a reduced effective interfacial diffusivity and a broadened release-time distribution. We discuss the results in terms of diffusion barrier physics, heterogeneous interfacial energetics, and coarse grained transport models that map microstructural coating parameters to macroscopic persistence (AUC).

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