Sudah Osama S, Arratia Paulo E, Coffin-Beach David, Muzzio Fernando J
Department of Chemical and Biochemical Engineering, Rutgers University, 98 Brett Road, Piscataway, New Jersey 08855, USA.
Drug Dev Ind Pharm. 2002 Sep;28(8):905-18. doi: 10.1081/ddc-120006423.
Experiments were conducted to determine the influence of process parameters such as fill level, mixing time, shear, and baffle presence along with material attributes such as initial active aggregate size and concentration on the homogeneity of a cohesive placebo formulation in a pilot plant scale tote blender. The formulation was a ternary system made up of microcrystalline cellulose, NaCl or KCl salt, and magnesium stearate. Blend homogeneity was evaluated by sampling the blend using core samplers. Salt concentration was quantified using a conductivity technique. After a brief transient mixture, homogeneity became insensitive to mixing time and initial active concentration, however, it was a strong function of fill capacity and initial active aggregate size. Sixty percent fill was found to be optimum. Active aggregate size had an adverse effect on mixture homogeneity. The best results were obtained when the salt aggregates were initially comparable in size to that of the excipient and a high shear pre-blending step was implemented prior to dilution in the tote blender. For the strongly agglomerating material examined here, pre-blending was only beneficial if the initial aggregate size was relatively small. For cohesive systems that form large and rigid aggregates, it is recommended to mill or screen the potentially agglomerating component and then mix the system in a blender equipped with an intensifier bar.
开展实验以确定工艺参数（如装料水平、混合时间、剪切力和挡板的存在）以及材料属性（如初始活性聚集体尺寸和浓度）对中试规模料仓式搅拌机中粘性安慰剂制剂均匀性的影响。该制剂是由微晶纤维素、氯化钠或氯化钾盐以及硬脂酸镁组成的三元体系。通过使用岩心取样器对混合物进行取样来评估混合均匀性。使用电导率技术对盐浓度进行定量。在短暂的瞬态混合后，均匀性对混合时间和初始活性浓度不敏感，然而，它是装料量和初始活性聚集体尺寸的强函数。发现60%的装料量是最佳的。活性聚集体尺寸对混合物均匀性有不利影响。当盐聚集体的初始尺寸与辅料的尺寸相当，并且在料仓式搅拌机中稀释之前实施高剪切预混合步骤时，可获得最佳结果。对于此处研究的强团聚材料，只有当初始聚集体尺寸相对较小时，预混合才有益。对于形成大而硬聚集体的粘性体系，建议研磨或筛选潜在的团聚组分，然后在配备增强棒的搅拌机中混合该体系。
