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

Among different technological variables that influence drug release from hydrophilic 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 different proportions of polymer content as well as with different proportions of admixed carboxymethylcellulose (CMC) in the range up to 35% (based on the total polymer content). The matrices release behavior was examined by absorption 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 proportions 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 buffer. The release mechanism in HCl is predominantly controlled by diffusion (n=0.46-0.62), while in phosphate buffer it is controlled, as reported previously, by diffusion/relaxation (n=0.58-0.85) and near zero order release at high CMC concentrations. Approximately doubling the total polymer content gives lower release rates for HCl in the range k=0.038-0.015 and for phosphate buffer k=0.0099-0.0034. Near zero order release is observed only at pH 7.4 (n=0.79-0.96). Decreasing release constant values show a logarithmic relationship with increasing values of the exponent n. This indicates that zero-order release occurs with sufficiently reduced release rate.