Blending Botanical Materials for Maximum Manufacturing Efficiency

Although one of the quickest steps in manufacturing, blending is also one of the most critical. Like painting a room, it is more about the extent of the preparation than about the process itself. Numerous variables are taken into consideration beforehand to ensure a short 10-minute botanical blend delivers a product with good content uniformity, good flow and the appropriate density. Each of these factors determines whether the final dosage delivers the intended amount of active component(s) to the end user.

Content uniformity, or ensuring that a blend is thoroughly homogeneous, is critically important. It is said that a blend must reach a perfect state of randomness in order to be truly uniform. There are several considerations to ensuring content uniformity.

The first is blender type and size. Rotating double cone or Vtype blenders are preferred over stationary blenders with inner rotating blade because they are less likely to have dead spots or corners where the blade does not reach. A second consideration in blender choice is the available headspace when fully loaded. A good rule of thumb is to fill a blender to no more than 80 percent of its total capacity, allowing enough room for the product to move while the blender is in motion.

It is also important to consider the physical property of each ingredient. An ideal blend consists of ingredients all with similar particle size, shape and density. If the ingredients are physically different, it will be more difficult to achieve good content uniformity. For example, mixing a very coarse granular product with a very fine powder is not desirable. Even if a good blend is obtained, the ingredients may actually begin to separate or settle during transit or with the vibration inside a feeder hopper.

The amount of each ingredient also impacts homogeneity. It can be difficult to achieve a good blend when the formula calls for a mixture of mostly one ingredient with a very small quantity of a second ingredient. If the quantities going into the blend are dissimilar, one or more pre-blending or pre-mixing steps may be required. This process is also known as a geometric dilution or pyramiding. The idea is to come up with a mixing plan and complete the blend in multiple steps of increasing quantity. If the quantities are very dissimilar, the premixing step can be repeated several times. Each time, similar quantities of ingredients are combined and added to the blender until ultimately all of the components are incorporated into one final blend.

Good flow

is the second critical component that is directly related to good weight control in a finished dosage. Consistent weight is important because the formula is designed to deliver a certain amount of active ingredient(s) in a dosage of pre-determined weight (i.e. all tablets must weigh 600 mg to deliver 500 mg of active(s)). If the dosage weight is inconsistent, it is likely to not deliver the intended amount of active(s). In order to get a consistent fill weight, the powder must flow like a liquid. When poured out of a container like water, the powder should drop in a steady uninterrupted stream.

Particle shape and size distribution are particular concerns in flow. Botanical powders, particularly barks and roots, are notorious for needle-like fibers. These typically inhibit flow and ultimately cause problems. The best way to minimize the presence of fibers is to mill the powder to a very fine particle size prior to blending.

The ideal particle size for the majority of solid dosage applications typically falls under a bell-shaped curve ranging from a U.S. standard 20-200 mesh. An excessive amount of particles bigger than 20 mesh can cause surface mottling and weight variation in your final dosage. An excessive amount of particles smaller than 200 mesh can inhibit flow; also leading to weight variation.

Other issues that pose challenges in flow, particularly with botanicals, are moisture absorption, oiliness, waxy consistency and static electricity. All of these factors inhibit flow by causing the product to become clumpy, gritty or sticky. The most common solution is to add a glidant. Glidants have an extremely small particle size (140 to 400 mesh) and work by coating the surface of larger particles to reduce friction, absorb excess moisture and enhance flow. Examples of glidants are silicone dioxide, calcium silicate and talc.

Density

becomes a critical parameter if you have trouble achieving the desired target weight of your finished dosage. For example, you design a formula such that 600 mg of blend will contain 500 mg of active(s) plus 100 mg of filler. Then you discover the heaviest tablets you can make or the most that can fit in the gelatin capsule is 550 mg, because the product is too fluffy. Two options to modify density are replacement of fillers or granulation.

Interchanging low-density fillers for those with a higher density is an economical way of increasing overall density and achieving the target dosage weight. Replacing some low density MCC (microcrystalline cellulose) with high density DCP (dicalcium phosphate) may be enough to fix the problem.

Depending on the process selected, density can be either increased or decreased through granulation. The most common methods for density increase are wet granulation and roller compaction. Fluid bed agglomeration is best suited to decrease density. A common solution for the weight problem would be to granulate your active(s) to increase density, and an added side benefit of granulation is that fewer fillers are required and can be removed from the formula.

Now that you have selected your blender, determined a load size, examined the percentages and physical properties of each ingredient (possibly pre-milled, preblended and granulated), you are ready for your simple 10-minute blend. Enjoy the short break.

Emilio Gutierrez , vice president of operations, BI Nutraceuticals-East (www.botanicals.com), has more than 17 years experience in both the pharmaceutical and nutritional industries. He specializes in the design and production of bulk powder and solid dosages, has held numerous positions in manufacturing, product development and technical sales, and holds two patents in powder processing. Gutierrez holds a degree in pharmacy from Rutgers University, where he is also a guest lecturer, and an MBA degree in Management from Iona College.