MULTIPLE-LAYER COMPRESSION-COATED TABLETS - FORMULATION AND HUMIDITY STUDIES OF NOVEL CHEWABLE AMOXICILLIN CLAVULANATE TABLET FORMULATIONS/

The purpose of this study was to produce novel multiple-layer, compres sion-coated, chewable tablet formulations containing amoxicillin trihy drate, and clavulanic acid as potassium clavulanate, and to test in vi tro dissolution characteristics and the effect of humidity stability c ompared to Augmentin(R) chewable tablets as a reference. Double- and t riple-layer tablets were manufactured on a laboratory scale by multipl e-layer dry compression, and dissolution profiles of both active ingre dients were determined. Tablets were subjected to stability evaluation in laboratory-scale humidity tanks maintained at constant humidity. A ssay of content was determined by HPLC or UV spectroscopy. Physical ch aracteristics of the powder mixture, such as angle of repose and of ta blets for hardness and friability, were also determined. Chewable tabl ets showed similar dissolution profiles in vitro for both active ingre dients, compared to the marketed reference, Augmentin. The stability o f clavulanic acid, but not amoxicillin, was increased in the novel tri ple or bilayer formulation. The tablets showed suitable friability, ha rdness, and angle of repose for starting materials to suggest that ind ustrial scale-up is feasible. This approach to formulation of drugs co ntaining multiple or moisture-sensitive ingredients has been shown to increase the stability of the central core drug without changing the d issolution pattern of the active ingredients. This formulation is expe cted to be Bioequivalent in vivo based on these in vitro results.