Thermodynamic Eigenrate Decomposition for Drug Release from Electrospun Fibrous Matrices: Plain-Polymer, Cyclodextrin-Complexed, and Experimentally Informed Formulations
Theoretical modeling study demonstrates accurate drug release prediction in electrospun fibrous matrices, indicating robust mechanistic separation of diffusion, swelling, and erosion.
Key Points
To establish and validate a thermodynamic framework, the Modified Multicomponent Interactive Release model, that predicts drug release kinetics across diffusion, swelling, and erosion mechanisms in electrospun matrices.
Formulated the M-MIR framework using Hansen solubility parameters, Flory–Huggins interaction parameters, and a Flory–Rehner swelling criterion to quantify mechanistic weights and identify mat half-thickness as the diffusion length.
Validated the model across three formulation tiers using published release datasets for naproxen in poly(ε-caprolactone) nanofibers (plain and cyclodextrin-complexed) and ciprofloxacin/rutin co-release from crosslinked PVA/chitosan membranes.
In non-swelling poly(ε-caprolactone) nanofibers, an interaction parameter of 9.75 closed the swelling gate to fix diffusion weight at 1.0, resolving cyclodextrin complexation into a 65% drop in effective diffusivity and a 2.45-fold increase in the transport constant.
In swelling PVA/chitosan membranes, swelling dominated drug release with mechanistic weights of 0.58 to 0.69, ranking first across all three release profiles while maintaining non-negative mechanistic parameters.