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.
Juárez
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H
Pharmacy Department, National School of Biological Sciences, National Polytechnic Institute, Carpio y Plan de Ayala, Col. Santo Tomas, CP 11340, Mexico D.F.
Rico
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G
Villafuerte
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D015761:4-Aminopyridine / Q000737:chemistry*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004347:Drug Interactions; D005079:Excipients; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry*; D013607:Tablets
D005079:Excipients; D011480:Protease Inhibitors; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D015761:4-Aminopyridine; D002266:Carboxymethylcellulose Sodium