Improve homogeneity during powder blending; is there an expert

Improve homogeneity during powder blending; is there an expert

Powder to powder mixing is, admittedly, one of the most difficult operations in Pharmaceutical processing. I wish, the question was more specific. All the same, here are some general factors to keep in mind:

  1. Volumetric ratio of different powders being mixed
  2. Particle sizes - smaller the particle size, more are the particles available for the same weight, resulting in better distribution, especially of the smaller components.
  3. Relative densities of the components. This is usually overlooked but should be easy to appreciate. Density difference is the key cause of powder segregation.
  4. Flow characteristics. If one component is far better flowable than the other, mixing will be a real challenge. An example in kitchen: having to mix of mustard seeds and cumin (jeera) seeds!
  5. Choice of blender: Powder bulk with poor flow cannot be blended using a “tumbling blender” like, cone/drum/Octagonal blender. One has to use a blender with mixing blades, like planetary or ribbon or some other.
  6. To distribute very small components, one often resorts to ‘serial blending’ or ‘geometric mixing’. Personally, I stay away from “bag-mixing” for it is impossible to standardize, let alone validate!
  7. Another technique is to dissolve the very small component in suitable solvent and adsorb it on the larger component, while mixing. However, stability of the “solution” must be confirmed.

Hope, you can pick some clues from this. Good luck.

Thanks, Koshore for your elaborate answer to achieve blend uniformity.
I would suggest a few more as follows,

  • For material having static charge it is difficult to mix with the other material in powder form as it gets adhered to equipment surfaces, sieves, scoops, etc. Hence, it is of utmost importance to de-charge the static charge of that material by mixing it with inert material such as starch, talc or dibasic calcium phosphate so that this pre-mix can be easily blended ensuring uniformity. For example, Loperamide HCl, and Miconazole nitrate APIs have high static charge and hence it becomes a challenge to mix them with other powders uniformly.
  • The second challenge is to mix colors (dyes) with the dry mix (powders) before granulation in the tablet manufacturing process. Colors can be first mixed with inert materials such as starch, talc, or dibasic calcium phosphate in geometric proportion in a small blender. After achieving a uniform distribution of color material this premix should be mixed with the bulk blend. It is to be ensured that this color premix should be added in the blender in layers (sandwich pattern) for uniform mixing. It is important to ensure uniform color distribution in a blend before granulation. Otherwise, tablets will have color shade variation or mottled appearance (mosaic appearance).

This is in continuation with my previous communication about achieving uniform blending of dry mix.
In case of color (dye compound) material, it should be sieved along with inert material and then should be mixed geometrically in a small blender.
For example, Riboflavin (Vitamin B2) is bright yellow in color. Similarly, color dyes such as FDC Yellow 5, 7 & others (Tartrazine, Sunset yellow, Amaranth, Poceau 4R, Brilliant blue, etc.) can not be mixed uniformly if directly added in a small blender along with inert material for geometric mixing.

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