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

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 o f drug release from high drug-load controlled-release theophylline tablets have been examined. Drug release was satisfactorily described by a surface-erosion model that t akes into account the geometry of the tablet, differential radial and axial erosion rates, and the initial burst effect (r(2) > 0.99 for all formulati ons). The axial and radial erosion rate constants were inversely proportion al to the amount of magnesium stearate in the formulation (P < 0.0001). The most dramatic reductions in erosion rate occurred between 0 and 1% magnesi um stearate content. For magnesium stearate concentrations greater than or equal to 2.5% the ratio of radial to axial erosion rate constants was essen tially constant at 3 (approx.); however, for formulations with magnesium st earate less than or equal to 1% the ratio tended toward unity. Reducing mat rix porosity over the range 26 to 14% resulted in reduced erosion rates. Ho wever, a threshold of 17% (approx.) porosity was identified below which fur ther 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 matri x tablets containing sparingly soluble drugs, such as theophylline, magnesi um stearate at appropriate levels can modulate the erosion rate constants a nd act as an effective release-controlling excipient. Drug-release profiles are predictable and relatively robust in terms of changes in compaction ra te and applied force routinely encountered in large-scale tablet manufactur ing.