Homogeneity

By: Brandon Armstrong on May 28, 2015

With recent posts from Amit and Gary, it’s clear that the shared goal of the various processes is homogeneity. Webster will tell you that it is “the state of having identical cumulative distribution function or values.” Since no one’s making a dictionary with Watson products (…yet), rephrasing that to mean “consistent, uniform distribution of all ingredients in a product” is acceptable for this discussion.

The largest issue at play, particularly in the area of powdered mixes and tableting, is particle size. Gary’s post above does a fairly good job of explaining the issues and how to solve them. For an exaggerated illustration of this, imagine a drum full of bowling balls. Then imagine adding a bag of sand to the drum. Obviously, the sand flows between the larger balls, and settles to the bottom. In order to get that drum to be uniform, either the bowling balls would have to be reduced in size (via milling or micronizing) or the sand would have to be increased in size (via agglomeration/granulation). Without the large difference in particle size, our imaginary drum of sporting equipment and beach particles can be made into a uniform- though very odd- mixture. Whether particle size should be increased or decreased for a specific ingredient depends on the product and application. It should be noted that even with these tools at a formulator’s disposal, a range of particle sizes can be necessary for end product characteristics.

Another homogeneity challenge for formulators is the use of very tiny amounts of ingredients. While making a dilution blend of an ingredient can be effective, another approach is trituration. Another analogy can- hopefully- simplify the differences between the two. So, let’s say there are 100 third-graders going to play mini-golf. The first child off the bus is given a deep red golf ball, and the other 99 get plain white balls. This is an admittedly on-the-nose description of a blend to dilute an ingredient- in this case, a 1% blend. If those same third-graders came back the next day and all 100 were each given a light pink ball- that’s trituration. See, in the second field trip, the same amount of red paint was used for the golf balls, but rather than being used on one ball to make it deep red, it was split amongst all 100 and turned them pink. Averaged out, both sets of golf balls contain the same amount (1%) of red paint, but it’s far more uniform with the second approach. This is why trituration is so important for expensive ingredients, such as Vitamin B12, as a formulator can be much more certain of consistently meeting label claim without over fortifying and driving up the cost.

Somewhat related to trituration, for the sake of homogeneity, is spray drying. Unlike trituration, the active material and the substrate are in the same solution. Like trituration, it helps ensure uniformity of an active material by means of dilution with a substrate. There are other advantages to spray drying as well, but that’s another blog post.

These are just a few of the variables when it comes to homogeneity. Processing parameters, such as mixing time, play a large role. Individual product characteristics can vary greatly and have a very large impact as well. In short, while the goal- a homogeneous product- is the same, each product’s path can be wildly different.