Cross-sectional structure evolution of phase-separated spin-coated ethylcellulose/hydroxypropylcellulose films during solvent quenching

• Published in: RSC advances Vol. 12; no. 4; pp. 2678 - 2689
• Main Authors: Carmona, Pierre, von Corswant, Christian, Röding, Magnus, Srkk, Aila, Olsson, Eva, Lorn, Niklas
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 2022; The Royal Society of Chemistry
• Subjects: Chemistry; Controlled drug delivery; Cross-sectional structures; Cross-sections; Drug transport; Drug transport rates; Ethanol; Ethyl cellulose; Ethylcellulose; Evolution; Film thickness; Fluidized beds; Hydroxypro-pylcellulose; Hydroxypropyl cellulose; Image analysis; Industrial manufacturing process; Morphology; Pelletizing; Pellets; Phase diagrams; Phase-separated structures; Porous film; Scanning microscopy; Separation; Shrinkage; Solvents; Spin coating; Spraying; Structure evolution; Thin films; Transport rate; Watersoluble
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d2ra04178b

Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The films are applied on the pellets using fluidized bed spraying. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. However, a detailed understanding of the evolution of the phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process. This work aimed to understand the structure formation and film shrinkage during solvent evaporation. The cross-sectional structure evolution was characterized using confocal laser scanning microscopy (CLSM), profilometry and image analysis. The effect of the EC/HPC ratio on the cross-sectional structure evolution was investigated. During shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. This transition appears when the typical length scale of the phase-separated structure is on the order of the thickness of the film. This was particularly pronounced for the bicontinuous systems. The shrinkage rate was found to be independent of the EC/HPC ratio, while the initial and final film thickness increased with increasing HPC fraction. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and allow tailoring of thin EC/HPC films structure for controlled drug release. The EC/HPC/EtOH phase diagram could be estimated from the CLSM monitoring of the cross-sectional in situ phase separation. The findings of this work provide a good understanding of the structure evolution.