Fabrication and characterization of spin-coated multilayer surface-eroding implants for automated multi-pulse drug...

Medication nonadherence contributes to disease progression, avoidable hospitalization, and an estimated $100-300 billion in annual excess healthcare costs in the United States. Implants that encode a dosing schedule during fabrication offer an alternative to patient-dependent administration. Here we apply spin coating to build multilayer surface-eroding implants from cellulose acetate phthalate (CAP) and Pluronic F-127, stacking fluorescein-loaded poly(vinyl alcohol) active layers between degradable CAP-Pluronic composite (CAPP) barrier layers whose thickness sets the interval between release events. Spin-curve calibration gave an inverse power-law dependence of thickness on rotational speed (R² = 0.979) from 436 ± 9 to 92 ± 4 μm. Against solvent-cast films produced from a necessarily different formulation at a matched 400 μm nominal target, spin coating reduced batch-to-batch standard deviation from approximately 34 to 2 μm and within-film standard deviation from 43-47 to 5-12 μm (n = 3 independently fabricated films per method); at a 100 μm target it reduced the maximum surface excursion below the mean plane, measured by atomic force microscopy, from 146.1 to 4.5 nm; confocal Raman mapping showed the standard deviation of the CAP/F-127 peak-height ratio falling from 2.91 to 0.77. Two device configurations, designated Q16 and Q72 after the approximately 16 and 72 h inter-pulse intervals they produced, each gave three discrete release events with near-baseline inter-pulse signal (n = 6 devices per condition).