Characterization of pore structure of polymer blended films used for controlled drug release Henrike Häbel a,f, ⁎, Helene Andersson b,c,f , Anna Olsson d,f , Eva Olsson d,f , Anette Larsson e,f , Aila Särkkä a,f a Chalmers University of Technology and University of Gothenburg, Department of Mathematical Sciences, SE-412 96 Gothenburg, Sweden b SP Food and Bioscience, Structure and Material Design, Box 5401, SE-402 29 Gothenburg, Sweden c Chalmers University of Technology, Department of Materials and Manufacturing Technology, SE-412 96 Gothenburg, Sweden d Chalmers University of Technology, Department of Applied Physics, SE-412 96 Gothenburg, Sweden e Chalmers University of Technology, Department of Chemistry and Chemical Engineering, SE-412 96 Gothenburg, Sweden f SuMo BIOMATERIALS, VINN Excellence Center, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden abstract article info Article history: Received 25 August 2015 Received in revised form 2 December 2015 Accepted 8 December 2015 Available online 11 December 2015 The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross- sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead character- izing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies. © 2015 Elsevier B.V. All rights reserved. Keywords: Pore shape Permeability Image processing Porous material Scanning electron microscopy 1. Introduction Porous polymer blended films are often used as pharmaceutical coatings since they can provide a wide range of structures with different properties favorable for controlled drug release [1]. In order to under- stand and control mass transport properties like permeability, it is essential to characterize the pore structure within such films. While methods to experimentally study the porosity of a material have long been available [2], today's imaging techniques such as scanning electron microscopy (SEM) open up new opportunities to characterize the pore structure with more attention to details using tools from image analysis including, for instance, binarization and pore boundary detection [3,4]. These tools can be used to study porosity and pore shape. The pore shape, in turn, can be related to pore tortuousity and connectivity, which have previously been identified as important factors affecting mass transport and overall releasability of a drug [5]. Therefore, the development of appropriate image processing procedures to extract the pore structure and perform statistical image analysis of its detailed characteristics have become of large interest. In this article, we statistically compare pore characteristics of blend- ed films of two of the most common cellulosic polymers used in controlled release formulations, namely ethyl cellulose (EC) and hydroxypropyl cellulose (HPC). Such bio-based films are non-toxic, non-allergenic and have good film forming properties and stability [6]. Whereas EC is water insoluble, HPC is generally soluble in water or in the gastrointestinal tract at room temperature (0-solvent at about 41 °C) and can be used as a pore former [7]. The two polymers are dissolved in a common solvent, which evaporates during film spraying resulting in phase separation. In this way the film structure forms and the pores result from subsequent HPC leaching [8,9]. Hence, the HPC-rich domains serve as a template for pores and determine their size and shape. There are several factors influencing the formation of the pore structure of EC/HPC films such as film processing parameters [8], polymer blend composition [6] and polymer viscosity grade [10]. Journal of Controlled Release 222 (2016) 151–158 ⁎ Corresponding author. E-mail address: henrike.habel@chalmers.se (H. Häbel). http://dx.doi.org/10.1016/j.jconrel.2015.12.011 0168-3659/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel