Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 65, Issue 1, Pages 85-93Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2006.07.010
Keywords
floating-pulsatile drug delivery; calcium pectinate beads; diclofenac sodium; hollow beads; gamma scintigraphy; chronotherapy
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The purpose of this work was to develop hollow calcium pectinate beads for floating-pulsatile release of diclofenac sodium intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic crosslinking. The floating beads obtained were porous (34% porosity), hollow with bulk density < 1 and had F-t50% of 14-24 h. In vivo studies by gamma scintigraphy determined on rabbits showed gastroretention of beads up to 5 h. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. This approach suggested the use of hollow calcium pectinate microparticles as promising floating-pulsatile drug delivery system for site- and time-specific release of drugs acting as per chronotherapy of diseases. (c) 2006 Elsevier B.V. All rights reserved.
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