Novel Method for Visualizing Water Transport Through Phase-Separated Polymer Films

Olsson

et al. 2020

Journal of Microscopy

Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography is a well-established technique for high resolution imaging and reconstruction of the microstructure of a wide range of materials. Segmentation of FIB-SEM data is complicated due to a number of factors; the most prominent is that for porous materials, the scanning electron microscope image slices contain information not only from the planar cross-section of the material but also from underlying, exposed subsurface pores. In this work, we develop a segmentation method for FIB-SEM data from ethyl cellulose porous films made from ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. These materials are used for coating pharmaceutical oral dosage forms (tablets or pellets) to control drug release. We study three samples of ethyl cellulose and hydroxypropyl cellulose with different volume fractions where the hydroxypropyl cellulose phase has been leached out, resulting in a porous material. The data are segmented using scale-space features and a random forest classifier. We demonstrate good agreement with manual segmentations. The method enables quantitative characterization and subsequent optimization of material structure for controlled release applications. Although the methodology is demonstrated on porous polymer films, it is applicable to other soft porous materials imaged by FIB-SEM. We make the data and software used publicly available to facilitate further development of FIB-SEM segmentation methods.

Section: Methodsmentioning

confidence: 99%

Three‐dimensional reconstruction of porous polymer films from FIB‐SEM nanotomography data using random forests

Röding

Olsson

et al. 2020

Journal of Microscopy

“…Phase‐separated films are produced as follows. Three solutions of EC (Ethocel Standard premium, viscosity 10 cP, Dow Wolff Cellulosics GmbH) and HPC (Klucel Pharm HPC, viscosity grade LF) with 95% ethanol as solvent 24–26 are prepared. All have 6% (w/w) polymer (total polymer concentration for EC and HPC combined), and the weight fractions of HPC are 22%, 30% and 45%.…”

Section: Methodsmentioning

confidence: 99%

Convolutional neural networks for segmentation of FIB‐SEM nanotomography data from porous polymer films for controlled drug release

Skärberg

Mendoza-Lara

et al. 2021

Journal of Microscopy

Self Cite

Phase‐separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water‐soluble HPC phase produces an EC film with a porous network through which the drug is transported. The drug release can be tailored by controlling the structure of this porous network. Imaging and characterization of such EC porous films facilitates understanding of how to control and tailor film formation and ultimately drug release. Combined focused ion beam and scanning electron microscope (FIB‐SEM) tomography is a well‐established technique for high‐resolution imaging, and suitable for this application. However, for segmenting image data, in this case to correctly identify the porous network, FIB‐SEM is a challenging technique to work with. In this work, we implement convolutional neural networks for segmentation of FIB‐SEM image data. The data are acquired from three EC porous films where the HPC phases have been leached out. The three data sets have varying porosities in a range of interest for controlled drug release applications. We demonstrate very good agreement with manual segmentations. In particular, we demonstrate an improvement in comparison to previous work on the same data sets that utilized a random forest classifier trained on Gaussian scale‐space features. Finally, we facilitate further development of FIB‐SEM segmentation methods by making the data and software used open access.

“…Previous work detailing the 3-D microstructure of this type of EC/HPC polymers can be found in Marucci et al 16,17 and in Andersson et al, 18 where the material has been imaged using confocal microscopy and scanning electron microscopy. Transport through these coatings has been visualized using in situ environmental scanning electron microscopy in Jansson et al 19 The same type of polymer has also been characterized with respect to pore shape and branching points in H€ abel et al, 20,21 and a visualization of the interconnectivity of the three films which are used in this work can be found in Fager et al 22 In the present paper, we used our new measures, together with local porosity, pore size with respect to spheres, circles and lines, constrictivity measures, and measures based on distances through the pore structure, to extract important features of the pore geometry of 3-D images of EC/ HPC films. The images were obtained from combined focused ion beam and scanning electron microscopy (FIB-SEM) tomography of films where the aqueous soluble HPC phase had been leached, leaving the EC porous network intact.…”

Section: Introductionmentioning

confidence: 99%

New Characterization Measures of Pore Shape and Connectivity Applied to Coatings used for Controlled Drug Release

Barman

Journal of Pharmaceutical Sciences

Röding

et al. 2021

Self Cite

Pore geometry characterization-methods are important tools for understanding how pore structure influences properties such as transport through a porous material. Bottlenecks can have a large influence on transport and related properties. However, existing methods only catch certain types of bottleneck effects caused by variations in pore size. We here introduce a new measure, geodesic channel strength, which captures a different type of bottleneck effect caused by many paths coinciding in the same pore. We further develop new variants of pore size measures and propose a new way of visualizing 3-D characterization results using layered images. The new measures together with existing measures were used to characterize and visualize properties of 3-D FIB-SEM images of three leached ethyl-cellulose/hydroxypropyl-cellulose films. All films were shown to be anisotropic, and the strongest anisotropy was found in the film with lowest porosity. This film had very tortuous paths and strong geodesic channel-bottlenecks, while the paths through the other two films were relatively straight with well-connected pore networks. The geodesic channel strength was shown to give important new visual and quantitative insights about connectivity, and the new pore size measures provided useful information about anisotropies and inhomogeneities in the pore structures. The methods have been implemented in the freely available software MIST.