Production of inert cushioning beads: effect of excipients on the physicomechanical properties of freeze-dried beads containing microcrystalline cellulose produced by extrusion-spheronization.
Conventional highly compactible fillers such as microcrystalline cellulose (MCC) can be mixed with drug-loaded membrane-coated beads and compressed to form a tablet. However, due to particle size differences, there is substantial risk of segregation leading to weight variation and content uniformity problems. Furthermore, whenever modified release beads are included in a tablet matrix, care must be taken to assure the integrity of the coated beads. This paper describes the development of placebo beads containing MCC whose properties make them uniquely suitable for tableting modified release beads. These placebo beads have high compactibility and the ability to rapidly disintegrate. They deform readily and may provide a high degree of protection to drug-loaded membrane-coated beads during compression ('cushioning effect'). They can be produced in size ranges that provide minimal segregation propensity. Beads containing different MCC/lactose ratios and different types and levels of superdisintegrants were produced by extrusion-spheronization followed by freeze drying. The presence of high levels of MCC and different superdisintegrants, especially croscarmellose sodium, increased the granulation liquid requirement, thus producing freeze-dried beads with higher porosities and compactibility. Athy-Heckel analysis studies revealed that beads rich in MCC exhibited lower mean yield pressures than those containing high levels of lactose. The freeze-dried beads exhibited both plastic deformation and brittle fracture characteristics.