Influence of admired polymers on the metronidazole release from hydroxypropyl methylcellulose matrix tablets

Among different technological variables that influence the release from hydrophilic matrices, the use of mixtures of polymers represents a potential way of achieving the required release properties. Tablets of metronidazole-hydroxypropyl methylcellulose (HPMC) were prepared with a total polymer content of 10%. The influence on release behavior of added quantities of carboxymethylcellulose (CMC) corresponding to 1, 3, 5, 7 and 9%, referring to the total polymer content, has been examined. The influence of ethylcellulose (EC) proportions corresponding to 1, 3, 5, 7, 9, 10, 30 and 50%, referring to the total poly;mer content, has been also examined. The dissolution behavior was evaluated with USP 23 apparatus 2 (paddle) at 100 rpm and using 0.1 N HCl as a medium; through the absorption of samples at 277 nm. Addition of CMC produced a biphasic lineal kinetics. Before the transition point, increasing proportions of CMC in the polymer mixture led to decreasing dissolution rates (41-16%/h). This allowed the 'free' dissolution of about one half of the total metronidazole content (55%), independent of the polymer composition. After the transition point, increasing proportions of CMC led to decreasing dissolution rates (5.1-3.7%/h) controlled by diffusion through the hydrated gel matrix. The transition between the two lineal phases of the release profile increased with increasing CMC ratios (1.2-2.6 h). These results are the consequence of the obstruction created by the insoluble CMC (0.1 N HCl) that is enclosed and bound to HPMC. Addition of EC produced no change in the Higuchi type release pattern from the matrix. Increasing proportions of EC corresponded to release rates that first decreased (1, 3, 5, 7, 9 and 10% EC; 34-27%/h( 1/4 )) and then increased (10, 30 and 50% EC; 27-42%/h( 1/4 )). These results are supposed to be the consequence of metronidazole diffusion through interparticle pores and channels created by EC particles loosely bound to HPMC, after percolation of void spaces at a critical EC concentration of approximately 13.8%.