TY - JOUR
T1 - Influence of admixed carboxymethylcellulose on release of 4-aminopyridine from hydroxypropyl methylcellulose matrix tablets
AU - Juárez, Haydee
AU - Rico, Giovanna
AU - Villafuerte, Leopoldo
PY - 2001/3/23
Y1 - 2001/3/23
N2 - 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.
AB - 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.
KW - 4-Aminopyridine
KW - Carboxymethylcellulose
KW - Hydroxypropyl methylcellulose
KW - Matrix tablets
KW - Polymer mixtures
KW - Release mechanism
UR - http://www.scopus.com/inward/record.url?scp=0035937464&partnerID=8YFLogxK
U2 - 10.1016/S0378-5173(01)00583-X
DO - 10.1016/S0378-5173(01)00583-X
M3 - Artículo
SN - 0378-5173
VL - 216
SP - 115
EP - 125
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -