Influence of admixed carboxymethylcellulose on release of 4-aminopyridine from hydroxypropyl methylcellulose matrix tablets

Among different technological variables that influence drug release from hy drophilic matrices, the use of mixtures of polymers represents a potential way of achieving a variety of release properties. Tablets of the model drug 4-aminopyridine with hydroxypropyl methylcellulose were prepared with diff erent proportions of polymer content as well as with different proportions of admired carboxymethylcellulose (CMC) in the range up to 35% (based on th e total polymer content). The matrices release behavior was examined by abs orption of samples at 261 nm (USP 23 apparatus 2, paddle, at 50 rpm) using 0.1 N HCl and 0.2 M phosphate buffer as dissolution media. Increasing propo rtions of CMC in the polymer mixture lead to decreasing dissolution rates, in a range of k = 0.094-0.036 for HCl and k=0.044-0.009 for phosphate buffe r. The release mechanism in HCl is predominantly controlled by diffusion (n = 0.46-0.62). while in phosphate buffer it is controlled, as reported prev iously, by diffusion/relaxation (n = 0.58-0.85) and near zero order release at high CMC concentrations. Approximately doubling the total polymer conte nt gives lower release rates for HCl in the range k = 0.038-0.015 and for p hosphate buffer Ii = 0.0099-0.0034. Near zero order release is observed onl y at pH 7.4 (n = 0.79-0.96). Decreasing release constant values show a loga rithmic relationship with increasing values of the exponent II. This indica tes that zero-order release occurs with sufficiently reduced release rate. (C) 2001 Elsevier Science B.V. All rights reserved.