Research paper Pore shape in the sodium chloride matrix of tablets after the addition of starch as a second component Yu San Wu a, * , Henderik W. Frijlink a , Lucas J. van Vliet b , Kees van der Voort Maarschalk a,c a Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands b Department of Imaging Science and Technology, Delft University of Technology, Delft, The Netherlands c Department of Pharmaceutics, Schering-Plough Corporation, Oss, The Netherlands article info Article history: Received 16 February 2008 Accepted in revised form 19 May 2008 Available online 7 June 2008 Keywords: Pore shape Porosity Tablet strength Pore structure Binary mixture abstract The present research aims to test the hypothesis that the addition of a minor component causes a change in pore shape in the matrix of the primary component, causing a decrease in mechanical strength. Tablets made of sodium chloride only and tablets made of a mixture of sodium chloride (97.5% v/v) and starch (2.5% v/v) were compared. Tablets were subjected to a heat treatment to remove the starch. The pore structure was evaluated with mercury porosimetry and image analysis on SEM images. At comparable porosities the tensile strength of the mixture tablets was significantly lower than that of the tablets made of NaCl only. Visual inspection of the images suggested a structure with less connectivity of the grains for the heat treated mixture tablets. This was confirmed by the results of the algorithm calculating the rel- ative path length. Image analysis showed that the pore size distribution shifted towards larger pores after the addition of starch. It was thus concluded that the lower mechanical strength of the tablets made of the binary mixture was caused by the more open pore structure and more larger pores as could be detected with image analysis. Ó 2008 Elsevier B.V. All rights reserved. 1. Introduction Tablets that are produced in the pharmaceutical industry usu- ally consist of more than one component. All components in a tab- let influence tablet properties, such as mechanical strength or disintegration. It is therefore of great importance to understand the possible interaction between tablet excipients and to investi- gate how this affects tablet properties. Even in mixtures consisting of only two components, binary mixtures, it is not always easy to predict the properties of the tablets made of a certain composition. Research on the mechanical strength of tablets consisting of binary mixtures is described in numerous papers [1–9]. These pa- pers generally focus on mixing rules or the percolation theory [10]. It has also been suggested that the shape of the pores is an impor- tant factor determining the mechanical strength of tablets. This hypothesis was developed in a research project focusing on tablets made of a binary mixture of sodium chloride and starch [11]. It was found that the addition of small amounts of starch caused a signif- icant decrease in the strength of the sodium chloride matrix. Fur- ther measurements on the pore size distribution led to the hypothesis that the addition of the second component caused a change in the shape of the pores, which in turn was the main cause of the decrease in mechanical strength. It was the aim of the present research to investigate whether the addition of a minor component causes a change in pore shape of a matrix of sodium chloride and how this influences its strength. This was done by comparing two groups of tablets; tablets made with sodium chloride only and tablets produced from a mixture of 97.5% v/v sodium chloride and 2.5% v/v starch. All tablets under- went a heat treatment. In case the tablets contained starch the heat treatment was used to remove the starch. The tablets with only so- dium chloride underwent a heat treatment as a control to rule out the possibility that the heat treatment caused a change in mechan- ical strength of the sodium chloride matrix. The end porosities of all tablets were the same. 2. Materials and methods 2.1. Materials The particle size fractions of 75–106 lm of potato starch (Paselli MD10, DMV, Veghel, The Netherlands) and the particle size frac- tion of 106–150 lm of sodium chloride (Chemically pure quality, Akzo Nobel, Hengelo, The Netherlands) were used. The fractions were obtained by 30 min vibratory sieving (Fritsch analysette 3, Germany) and 12 min air jet sieving (Alpine A200, Augsburg, 0939-6411/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2008.05.028 * Corresponding author. Solvay Pharmaceuticals Building WNH, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. Tel.: +31 294 4777616. E-mail addresses: Yu-San.Wu@solvay.com, wysa2002@gmail.com (Y.S. Wu). European Journal of Pharmaceutics and Biopharmaceutics 70 (2008) 539–543 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb