Unit Product Design, Department Agriculture and Food, Division Bioeconomy and Health, RISE Research Institute of Sweden, Gothenburg, Sweden; Division Nano-and BioPhysics, Department of Physics, Chalmers University of Technology, Gothenburg, Sweden.
Wendelsbergs beräkningskemi AB, Mölnlycke, Sweden.
Int J Pharm. 2023 Sep 25;644:123350. doi: 10.1016/j.ijpharm.2023.123350. Epub 2023 Aug 26.
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.
多孔相分离乙基纤维素/羟丙基纤维素（EC/HPC）薄膜用于控制药物从药物丸中释放。水溶性 HPC 浸出并形成控制药物传输的多孔结构。在工业上，使用流化床喷涂装置对丸剂进行包衣，在浸出后得到具有不同孔隙率和结构的层状薄膜。在生产过程中，对多层、相分离结构的形成缺乏详细的了解。在这里，我们通过顺序旋涂研究了多层 EC/HPC 薄膜的形成，这是用来模拟工业过程的。使用先进的显微镜技术和图像分析研究了 EC/HPC 比和旋转速度对多层膜形成和结构的影响。进行了 Cahn-Hilliard 模拟以分析混合行为。由于在连续沉积循环中已经涂覆的层的粗化，在靠近基底表面的较大结构和靠近空气表面的较小结构处形成了梯度。发现多层膜的孔隙率随 EC/HPC 比和旋转速度而变化。混合行为的模拟和结构演化的原位表征表明，层的不混合可以解释不连续性和多层结构的起源。
