(673f) Lubrication in Continuous Tubular Powder Blenders

Granular mixing, based on the scale of mixing, can be generally classified as macro-mixing and micro-mixing. Macro-mixing is defined as the macro scale transport of particles or particle assemblies from one spatial co-ordinate to the other. It is responsible for most reduction in variance in unmixed powder streams. Micro-mixing is defined as mixing at the scale of a single particle. Micro-mixing is always associated with a change in the properties of individual particles [1].

The role of micro-mixing becomes particularly important in the presence of shear-sensitive ingredients, such as magnesium stearate, or other lubricants. Magnesium stearate, generally present as thin nanoparticles, is known to coat larger shear insensitive excipients and active ingredients [2]. This coating reduces the bonding ability of particles, and consequently makes it more difficult to process the material into tablets [3]. Magnesium stearate is also hydrophobic in nature and the coating of active ingredient particles by magnesium stearate results in increase in their hydrophobicity and consequently decrease in the dissolution rate of the active ingredient [4, 5]. Also observed is the improvement in packing efficiency of the coated materials (increased bulk density) and improved flow properties [3]. It is known that the coating extent of the shear sensitive material and consequently its associated effects are directly proportional to the total amount of strain experienced by the material. The greater the strain, the more pronounced is the extent of coating and consequently more pronounced are the associated effects [2-5]. Close attention is thus paid to the extent of lubricant mixing in traditional batch manufacturing to ensure that the lubricant is not subjected to excessive strain levels during the blending operation. Typically, shear-sensitive ingredients are added in a second stage, after the mixing of other ingredients, to minimize the strain they experience. Therefore, the bulk ingredients are blended for a few hundred revolutions in the blender before the lubricant is added to the system, and the lubricant is generally mixed for a few tens of revolutions.

This work presents a comparison between the amount of strain experienced by material in a typical batch blending process and a continuous blending process, specifically, in the presence of shear-sensitive ingredients, such as magnesium stearate. Findings show that the total amount of strain experienced by the in-process material in a batch tumbling blender is greater compared to that in a continuous paddle blender, under typical operating conditions. The higher strain experienced in batch processing necessitates the addition of shear sensitive materials, such as magnesium stearate, at a later stage in the blending operation, resulting in two-stages of ingredient addition. This may not be necessary in continuous operations due to the gentler nature of the process. It is also hypothesized that the material experiences a more uniform degree of shear in a continuous blender compared to a batch blender. Lastly, the effect of strain rate on blend lubricity is quantified. It was observed that the rate of strain addition does not have an impact on the lubricity of the final blend. Whereas the lubricity of the blend is only dependent on the total strain experienced by it.

References

1. Muzzio, F., Mixing Mechanics: Practical powder blending: Micromixing, in Powder and Bulk Engineering. 2016.

2. Pingali, K., et al., Mixing order of glidant and lubricant – Influence on powder and tablet properties. International Journal of Pharmaceutics, 2011. 409(1–2): p. 269-277.

3. Mehrotra, A., et al., Influence of shear intensity and total shear on properties of blends and tablets of lactose and cellulose lubricated with magnesium stearate. International Journal of Pharmaceutics, 2007. 336(2): p. 284-291.

4. Llusa, M., et al., Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients. Powder Technology, 2010. 198(1): p. 101-107.

5. Pingali, K., et al., Evaluation of strain-induced hydrophobicity of pharmaceutical blends and its effect on drug release rate under multiple compression conditions. Drug Dev Ind Pharm, 2011. 37(4): p. 428-35.