Porous phase-separated films made of ethylcellulose (EC) and hydroxypropylcellulose (HPC) are commonly used for controlled drug release. The structure of these thin films is controlling the drug transport from the core to the surrounding liquid in the stomach or intestine. However, detailed understanding of the structure evolution is lacking. In this work, we use spin-coating, a widely applied technique for making thin uniform polymer films, to mimic the industrial manufacturing process of fluidized bed spraying. The aim of this work is to understand the structure evolution and phase separation kinetics of single layer and multi-layer spin-coated EC/HPC films. The structure evolution is characterized using confocal laser scanning microscopy (CLSM) and image analysis.
The influence of spin-coating parameters and EC:HPC ratio on the final phase-separated structure and the film thickness was determined. Varying spin speed and EC:HPC ratio gave us precise control over the characteristic length scale and thickness of the film. The results show that the phase separation occurs through spinodal decomposition and that the characteristic length scale increases with decreasing spin speed and with increasing HPC ratio. The thickness of the spin-coated film decreases with increasing spin speed.
Furthermore, optimized spin-coating parameters were selected to study the kinetics of phase separation in situ, in particular the coarsening mechanisms and the time dependence of the domain’s growth as a function of EC:HPC ratio. We identified two main coarsening mechanisms: interfacial tension driven hydrodynamic growth for the bicontinuous structure and diffusion driven coalescence for the discontinuous structures. In addition, we obtained information on the wetting, the shrinkage, and the evaporation process by looking at a film cross section, which allowed an estimation of the binodal of the phase diagram.
The findings from this work give a good understanding of the mechanisms responsible for the morphology development and open the road towards tailoring thin EC/HPC film structures for controlled drug release.
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20 May, 2021, 10:00
20 May, 2021, 13:00