Incorporating Turbula mixers into a blending scale-up model for evaluating the effect of magnesium stearate on tablet tensile strength and bulk specific volume

Turbula bottle blenders are often used in lab-scale experiments during early-stage pharmaceutical product development. Unfortunately, applying knowledge gained with these blenders to larger-sized diffusion mixers is limited by the lack of blending models that include Turbula mixers. To address this need for lubrication blending scale-up, 2:1 blends of microcrystalline cellulose and spray-dried lactose or dibasic calcium phosphate were mixed with 1% magnesium stearate using Turbula bottle blenders, varying bottle volume, V (30-1250 mL); bottle headspace fraction, F-headspace (30-70%); and the number of blending cycles, r (24 to similar to 190,000 cycles). The impact of lubrication blending on tensile strength and bulk specific volume quality attributes, QA, was modeled by: QA/QA(0) =(1 - beta)+ beta exp(-gamma x L x F-headspace x r), where QA(0) is initial QA value, beta is sensitivity of QA to lubrication, gamma is formulation-specific lubrication rate constant, and L is characteristic mixing length scale (i.e. 1.5V(1/3) for Turbula blenders, V-1/3 for simple diffusion mixers). The factor of 1.5 captures the bottle dimensions and the more complex mixing dynamics of the Turbula blender. This lubrication blending process model is valid for scale-up from 30-mL to 200-L blenders. Assessing bulk specific volume may provide a simpler, more material-sparing means for determining gamma than tensile strength, since these QAs exhibited similar gamma values. (c) 2012 Elsevier B.V. All rights reserved.