International Journal of Pharmaceutics
Controlling the structure of spin-coated multilayer ethylcellulose/hydroxypropylcellulose films for drug release
Pierre Carmona, Jens Poulsen, Jan Westergren, Torben Nilsson Pingel, Magnus Röding, Eileen Lambrechts, Herlinde De Keersmaecker, Kevin Braeckmans, Aila Särkkä, Christian von Corswant, Eva Olsson, Niklas Lorén
Cahn-Hilliard simulations, Cellulose, Confocal laser scanning microscope, Electron microscopy, Multilayer film, Phase separation kinetics, Phase separation mechanisms, Porous film for controlled release
Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. Water-soluble HPC leaches out and forms a porous structure that controls the drug transport. Industrially, the pellets are coated using a fluidized bed spraying device, and a layered film exhibiting varying porosity and structure after leaching is obtained. A detailed understanding of the formation of the multilayered, phase-separated structure during production is lacking. Here, we have investigated multilayered EC/HPC films produced by sequential spin-coating, which was used to mimic the industrial process. The effects of EC/HPC ratio and spin speed on the multilayer film formation and structure were investigated using advanced microscopy techniques and image analysis. Cahn-Hilliard simulations were performed to analyze the mixing behavior. A gradient with larger structures close to the substrate surface and smaller structures close to the air surface was formed due to coarsening of the layers already coated during successive deposition cycles. The porosity of the multilayer film was found to vary with both EC/HPC ratio and spin speed. Simulation of the mixing behavior and in situ characterization of the structure evolution showed that the origin of the discontinuities and multilayer structure can be explained by the non-mixing of the layers.