Modeling of powder blending using on-line near-infrared measurements.

A model to quantify the degree of mixing in pharmaceutical powder mixing operations was developed. The additive volume mixing model is based on the determination of the characteristic volume of agitation for a given blender, which is dependent on process parameters such as the formulation ingredients, the geometry of the mixer, and the batch load. The calculation of this characteristic volume of agitation is based on the determination of the fitted fraction of formulation mixed after the first blender rotation. A variation of this model, denominated the iterative mixing model, was also developed. On-line near-infrared (NIR) measurements were taken throughout the runs to obtain the mixing profile and the dynamics of the powder bed as a function of blender rotations. Studies were conducted at two scales using two different formulations to study and compare the calculated characteristic volume of agitation for each blender-formulation system. This approach elucidates the existing relationship between the characteristic mixing parameters and critical rotations (required rotations to achieve content uniformity) for a given system and represents a step toward scale-up of solids mixing operations.