Influence of formulation and process variables on in vitro release of theophylline from directly-compressed Eudragit matrix tablets.
Extended-release theophylline (TP) matrix tablets were prepared by direct compression of drug and different pH-dependent (Eudragit L100, S100 and L100-55) and pH-independent (Eudragit RLPO and RSPO) polymer combinations. The influence of varying the polymer/polymer (w/w) ratio and the drug incorporation method (simple blend or solid dispersion) was also evaluated. Drug release, monitored using the Through Flow Cell system, markedly depended on both the kind of Eudragit polymer combinations used and their relative content in the matrix. Maintaining a constant 1:1 (w/w) drug/polymers ratio, the selection of appropriate mixtures of pH-dependent and pH-independent polymers enabled achievement of a suitable control of TP release. In particular, matrices with a 0.7:0.3 w/w mixture of Eudragit L100-Eudragit RLPO showed highly reproducible drug release profiles, with an almost zero-order kinetic, and allowed 100% released drug after 360 min. As for the effect of the drug incorporation method, simple blending was better than the solid dispersion technique, which not only did not improve the release data reproducibility, but also caused, unexpectedly, a marked slowing down in drug release rate.
Ceballos
A
A
Facultad de Farmacia, Universitad de Antioquia, 1226 Medellin, Colombia.
Cirri
M
M
Maestrelli
F
F
Corti
G
G
Mura
P
P
D000180:Acrylic Resins / Q000737:chemistry; D001993:Bronchodilator Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D015203:Reproducibility of Results; D012995:Solubility; D013607:Tablets; D013696:Temperature; D013806:Theophylline / Q000737:chemistry*
D000180:Acrylic Resins; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; C496966:Eudragit RSPO; D011108:Polymers; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D013806:Theophylline