Extrusion-spheronization of blends of Carbopol 934 and microcrystalline cellulose

We evaluated the effects of several process variable on the pharmaceutical an drug release properties of extrusion-spheronization pellets of blends of Carbopol 934 and microcrystalline cellulose (MCC) containing a high propor tion of Carbopol. The model drug was theophylline. Rheological monitoring d uring mixing was by mixer torque rheometry. Carbopol: MCC blends wetted wit h a CaCl2 solution showed different rheological behavior compared to blends with a high proportion of MCC wetted with water only. In contrast to previ ous suggestions, the optimal wetting point for extrusion did not coincide w ith the point of peak torque, but occurred just beyond this point, at much lower torque. The influence of process variables on blend properties was in vestigated with a three-variable factorial design (Carbopol: MCC ratio, wet ting liquid proportion, CaCl2: Carbopol ratio), and the influence of proces s variable on pellet properties with a four-variable design (the variables listed plus extrusion screen hole diameter). Blend torque values were stron gly influenced by CaCl2 proportion, while mean pellet diameter was influenc ed by Carbopol: MCC ratio. Mean pellet diameter also differed depending on whether the pellets contained theophylline. The observed among-formulation differences in theophylline release kinetics were largely explained by diff erences in pellet size and theophylline hydration state. Compaction of pell ets to form tablets markedly modified the drug release profile, making it b iphasic.