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

doi:10.1016/j.ijpharm.2023.123350

Controlling the structure of spin-coated multilayer ethylcellulose/hydroxypropylcellulose films for drug release

Int J Pharm. 2023 Sep 25:644:123350. doi: 10.1016/j.ijpharm.2023.123350. Epub 2023 Aug 26.

Authors

Affiliations

¹ 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.
² Wendelsbergs beräkningskemi AB, Mölnlycke, Sweden.
³ Unit Product Design, Department Agriculture and Food, Division Bioeconomy and Health, RISE Research Institute of Sweden, Gothenburg, Sweden.
⁴ Unit Product Design, Department Agriculture and Food, Division Bioeconomy and Health, RISE Research Institute of Sweden, Gothenburg, Sweden; Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.
⁵ Unit Product Design, Department Agriculture and Food, Division Bioeconomy and Health, RISE Research Institute of Sweden, Gothenburg, Sweden; Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium.
⁶ Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium; Ghent Light Microscopy Core, Ghent University, Ghent, Belgium.
⁷ Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium.
⁸ Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden.
⁹ Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden.
¹⁰ Division Nano-and BioPhysics, Department of Physics, Chalmers University of Technology, Gothenburg, Sweden.
¹¹ 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. Electronic address: niklas.loren@ri.se.

PMID: 37640089
DOI: 10.1016/j.ijpharm.2023.123350

Abstract

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.

Keywords: Cahn-Hilliard simulations; Cellulose; Confocal laser scanning microscope; Electron microscopy; Multilayer film; Phase separation kinetics; Phase separation mechanisms; Porous film for controlled release.

MeSH terms

Biological Transport
Cellulose*
Drug Liberation

Substances

hydroxypropylcellulose
ethyl cellulose
Cellulose