Abstract

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 openaccess.

Highlights

  • A common means of controlling the release of active pharmaceutical ingredients is to coat oral dosage forms with phase-separated polymer films

  • As in Röding et al.,[20] intensity gradients present in the x direction of the images are removed in the following fashion: we fit linear functions to the mean intensities of each data set as a function of the x-coordinate, using least squares

  • We have developed a segmentation method based on convolutional neural networks (CNNs) for focused ion beam and scanning electron microscope (FIB-SEM) data

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Summary

Introduction

A common means of controlling the release of active pharmaceutical ingredients is to coat oral dosage forms (tablets or pellets) with phase-separated polymer films. The resulting material is a film consisting of a water-insoluble EC matrix with a porous network through which the drug is transported by diffusion. The drug release can be efficiently controlled by tailoring the structure of such a porous network, as studied both in experiments and simulations.[1,2,3,4,5]. A detailed understanding of how to control and tailor film formation and drug release requires high spatial resolution imaging and accurate characterization of such EC porous films. Using FIB-SEM, a 3D region of interest is imaged using a slice and image procedure. The planar cross-section surface is imaged using the SEM. A FIBSEM tomography data set typically consists of a few hundred 2D SEM images acquired in this fashion

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