A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction

Jolliffe, Hikaru G. and Prostredny, Martin and Mendez Torrecillas, Carlota and Bordos, Ecaterina and Tierney, Colette and Ojo, Ebenezer and Elkes, Richard and Reynolds, Gavin and Song, Yunfei Li and Meir, Bernhard and Fathollahi, Sara and Robertson, John (2024) A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction. International Journal of Pharmaceutics, 659. 124232. ISSN 0378-5173 (https://doi.org/10.1016/j.ijpharm.2024.124232)

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Abstract

Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body of work around how lubrication via batch blender operation affects tablet critical quality attributes such as hardness and tensile strength. But, aside from being batch operations, the design of these blenders is such that they operate with low-shear, low-intensity mixing at Froude number values significantly below 0.4 (Froude number Fr being the dimensionless ratio of inertial to gravitational forces). The present work explores the performance of a mini-blender which has a fundamentally different mode of operation (static vessel with rotating blades around a mixing shaft as opposed to rotating vessel with no mixing shaft). This difference allows a substantially wider operating range in terms of speed and shear (and Fr values). The present work evaluates how its performance compares to other blenders studied in the literature. Tablet compaction data from blends produced at various intensities and regimes of mixing in the mini-blender follow a common trajectory. Model equations from literature are suitably modified by inclusion of the Froude number Fr, but only for situations where the Froude number was sufficiently high (1 < Fr). The results suggest that although a similar lubrication extent plateau is eventually reached it is the intensity of mixing (i.e. captured using the Froude number as a surrogate) which is important for the lubrication dynamics in the mini-blender, next to the number of revolutions. The degree of fill or headspace, on the other hand, is only crucial to the performance of common batch blenders. Testing using alternative formulations shows the same common trend across mixing intensities, suggesting the validity of the approach to capture lubrication dynamics for this system.

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