An investigation into the erosion behaviour of a high drug-load (85%) particulate system designed for an extended-release matrix tablet. Analysis of erosion kinetics in conjunction with variations in lubrication, porosity and compaction rate.

摘要

The effects of the amounts of lubricants (magnesium stearate 0-5% and talc 0-3%) and changes in compaction rate and tablet porosity on the mechanism of drug release from high drug-load controlled-release theophylline tablets have been examined. Drug release was satisfactorily described by a surface-erosion model that takes into account the geometry of the tablet, differential radial and axial erosion rates, and the initial burst effect (r2 > 0.99 for all formulations). The axial and radial erosion rate constants were inversely proportional to the amount of magnesium stearate in the formulation (P < 0.0001). The most dramatic reductions in erosion rate occurred between 0 and 1% magnesium stearate content. For magnesium stearate concentrations > or =2.5% the ratio of radial to axial erosion rate constants was essentially constant at 3 (approx.); however, for formulations with magnesium stearate < or =1% the ratio tended toward unity. Reducing matrix porosity over the range 26 to 14% resulted in reduced erosion rates. However, a threshold of 17% (approx.) porosity was identified below which further reductions in porosity resulted in only incremental changes in release rates. The rate of erosion and drug release was insensitive to changes in machine speed over the range 20 to 100 rev min(-1). For highly loaded matrix tablets containing sparingly soluble drugs, such as theophylline, magnesium stearate at appropriate levels can modulate the erosion rate constants and act as an effective release-controlling excipient. Drug-release profiles are predictable and relatively robust in terms of changes in compaction rate and applied force routinely encountered in large-scale tablet manufacturing.