Mixing of pharmaceutical powder is a unit operation that serves to make two or more components uniformly distributed in the powder bed. In most cases, solid dosage forms do not only contain one component. Several ingredients are combined together to serve different and specialized pharmaceutical purposes during manufacture, storage, or use.
For instance, a tablet formulation often consists of the drug substance and many other excipients, such as binders, bulking agents, disintegrants, lubricants, glidants, etc. As a result, the mixing process is necessary to ensure that the active pharmaceutical ingredient (API) and other components are homogeneously distributed throughout the tablet.
This article focuses on methods of mixing powders in small-scale operations.
Mechanisms involved in the mixing of pharmaceutical powder
There are three main mechanisms involved in the mixing process, related to the different kinds of particle motion. These include:
Mixing of Pharmaceutical Powders
There are four main methods of mixing powders in small-scale operations:
The trituration process involves direct rubbing or grinding of hard powder in a mortar and pestle. The trituration method is used for both pulverization and mixing. Two different types of mortar and pestle are commonly used:
- A Wedgewood mortar is used for pulverization and grinding because of its rough inner surface.
- A glass mortar is used for simple mixing and for mixing of coloured materials and dyes.
A powder spatula is used in the spatulation method, and the powders are mixed on a pill tile (ointment slab) or in a mortar. This method is adequate for mixing small amounts of powders and combinations of powders having the same densities.
The possible loss during transfer is minimal in this method, and mixing does not reduce the particle size. This method is used when there is a possibility of liquefaction during the mixing of two solid powders.
The sifting method is helpful for powders that resist mixing by trituration. Very light powders, such as magnesium oxide and charcoal, can be completely mixed by shaking them through a sieve.
Standardize prescription sieves are available, but an ordinary household flour sifter can be used effectively for this purpose. This process allows the removal of any large foreign bodies and agglomerates from the powder mix.
Tumbling is a process of mixing powders by shaking or rotating them in a closed container. This method is used when two or more powders have considerable density differences. This mode of mixing does not yield particle size reduction and compaction.
Wide-mouthed closed containers or zip-locked bags can be used when the powder volume should be within one third to one-half field. The powder mixture should flow freely in the air and avoid sliding the powder through the side of the container.
Homogeneity in large-scale mixing is achieved through the use of an appropriate mixer, which ensures the correct speed and sufficient time for mixing. Homogenous mixing is ascertained in a mixture when the concentration of each component in any region of the mixture is identical.
The mixing of pharmaceutical powders generally requires low shear rates; the mixers used for this purpose are planetary bowl mixers, high speed mixers, V blenders, ribbon/trough mixers, and rotating drum mixers.
Three basic rules for mixing pharmaceutical powders
- When mixing powders with different particle sizes (granular salt and fine powders), reduce each powder separately to fine particles before mixing.
- When mixing powders with different densities, put the light powder first and then put the heavier one on top of it.
- When mixing small amounts of a drug to a large volume of bulk powder, use the principle of geometric dilution.
When two powders with unequal quantities are mixed, the small weight (least weight) of the powder, usually the active ingredient is first triturated with an equal bulk of the diluting powder. This first dilution is then mixed with an equal portion of diluents. This process is repeated until all the powders are intimately mixed.
Example: Geometric dilution of one gram of a potent drug to be mixed with 20 g of the diluent lactose.
- First dilution: Mix 1 g drug with B1 g lactose (B2 g mixture).
- Second dilution: Mix 2 g of the first dilution with 2 g of lactose with trituration (B4 g mixture).
- Third dilution: Mix 4 g of the second dilution with 4 g of lactose with trituration (B8 g mixture).
- Fourth dilution: Mix 8 g of the third dilution with 8 g of lactose with trituration (B16 g mixture).
This process continues until the lactose is fully mixed with the blend.
- Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics – Basic Principles and Application to Pharmacy Practice. USA: Academic Press.