Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 355, Issue 1-2, Pages 259-268Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2007.12.038
Keywords
lamination; cross-linking; disintegration; barrier preservation; modified release
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Sodium alginate, a biopolymer, was employed in the formulation of matrix tablets. They cracked or laminated at acidic pH, compromising their dissolution performance. Improved mechanical strength and reduced barrier permeability of calcium alginate gel provided the rationale for cross-linking the alginate matrix to sustain drug release. Studies had suggested that the incorporation of soluble calcium salts in alginate matrix tablets could sustain drug release at near-neutral pH due to in situ cross-linking. However, results from the present study showed otherwise when gastrointestinal pH conditions were simulated. Significant reduction in drug release rate was only observed when an external calcium source was utilized at low concentration. High calcium ion concentrations caused matrix disintegration. In contrast, matrices pre-coated by calcium alginate could sustain drug release at pH 1.2 followed by pH 6.8 for over 12 h. The presence of cross-linked barrier impeded matrix lamination and preserved matrix structure, contributing to at least three-fold reduction in drug release at pH 1.2. Zero order release as well as delayed burst release could be achieved by employing appropriate grade of alginate and cross-linking conditions. (C) 2008 Elsevier B.V. All rights reserved.
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