RESUMEN
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.
Asunto(s)
Celulosa/química , Excipientes/química , Química Farmacéutica , Fuerza Compresiva , Liofilización/métodos , MicroesferasRESUMEN
The purpose of this study was to investigate the effect of granulating water level on the physical-mechanical properties of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC). Granulations containing either MCC or SMCC were manufactured at different water levels using a high-shear mixer and were then tray-dried. The water level ranged from 0 to 100%. The granules were evaluated for size, granular and true density, porosity, flow, compactibility, compressibility, and strain-rate sensitivity index (SRS). Increasing the water level affected the size, increased the granular density and flow properties of the granules, and decreased the porosity and compactibility. The compactibilities for both materials were similar and acceptable at each granulating water level up to 40%. They both showed poor compactibility at higher water levels. Yield values and SRSs revealed that MCC and SMCC have similar compressibility, and that both exhibit a plastic component to the deformation process. The granulating water level had no statistically significant effect on the compressibility or the SRS for MCC or SMCC. SMCC did not offer practical advantages over MCC, other than better flow in the powder form, which could be attributed to slightly larger particle size and the presence of silicon dioxide in its structure.