Research paper Liquid boundary movements in cylindrical and convex hydrophobic matrix tablets: Effects on tablet cracking and drug release Jari Pajander a, * , Bert van Veen b , Ossi Korhonen a , Reijo Lappalainen c , Jarkko Ketolainen a a Department of Pharmaceutics, University of Kuopio, Kuopio, Finland b Orion Pharma, Turku, Finland c BioMater Center, University of Kuopio, Kuopio, Finland Received 20 December 2005; accepted in revised form 18 May 2006 Available online 2 June 2006 Abstract The aim of this study was to investigate liquid penetration into both cylindrical and convex hydrophobic matrix tablets and to relate the changes in tablet structure to drug release. Starch acetate with degree of substitution of 2.7 was used as a hydrophobic matrix former and anhydrous caffeine as a freely soluble model drug. Phenolred was used as a colouring agent to enhance the visual detection of the liquid boundary movements, which were examined in axial and radial directions for both types of tablets. The tablets started to expand during the dissolution, resulting in cracking as the liquid boundary penetrated into tablet. The cracking influences drug release by short- ening the diffusion path and decreasing the tortuosity. The liquid boundaries proceed differently in cylindrical and convex tablets, this being attributable to differences in pore structure and density distribution. Cylindrical tablets are quite homogeneous in terms of density, but convex tablets have more porous areas at the domes of the tablet. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Hydrophobic matrix; Tablet; Starch acetate; Liquid boundary; Tablet cracking; Drug release 1. Introduction The oral route is the most common and convenient of the current administration routes for the systemic delivery of drugs. The most widely used solid dosage forms for con- trolled drug release purposes are tablets and these can be divided roughly into matrix and reservoir systems. Accord- ing to the Higuchi equation [1] for the release of a solid drug from a controlled release matrix tablet structure, the dissolution rate of the drug depends on many factors, including the exposed surface area and porosity of the matrix, and the tortuosity of the capillary system. The dis- solution of the drug compound, and furthermore, its release from the dosage form are related to the liquid pene- tration into the tablet. This is a parameter which is not completely understood. Starch acetates (SA) are modified starches produced by acetylating native starch [2]. The modification converts starch into a more hydrophobic derivative, as the average degree of substitution (DS) increases from 0 up to 3.0. Starch acetate is a suitable excipient for controlling drug release from tablets when DS is greater than 2.1 [3]. Although several studies [2–5] have been published attempting to establish the drug release from starch acetate matrices, until now the focus has been mainly on tableting and drug release kinetics. Previous studies [2,5] on starch acetate have demonstrated that crack formation takes place in SA matrix tablets during dissolution. Since drug dissolution after the burst of the tablet is initiated by the penetration of bulk liquid into the matrix structure, more focused research is needed to understand the relationships between physical changes which take place during dissolu- tion and the liquid movement in the tablet structure. 0939-6411/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2006.05.011 * Corresponding author. Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. Tel.: +358 17 163 305; fax: +358 17 162 252. E-mail address: pajander@hytti.uku.fi (J. Pajander). www.elsevier.com/locate/ejpb European Journal of Pharmaceutics and Biopharmaceutics 64 (2006) 167–172