Optimizing precision blending of tablets

Tumble blender technology can enhance the speed and homogeneous blending of tablets and
capsules with trace levels of additives

By Gregg Muench, Vice President of Business Development, GEMCO

May 02, 2019

To meet stringent regulatory requirements, such as the United States Pharmacopeia (USP), National
Formulary (NF) or U.S. Food & Drug Administration (FDA), as well as production and budgetary
demands, pharmaceutical manufacturers require high-volume precision blending of formulations on
equipment that provides exceptional batch-to-batch consistency and repeatable results.

When manufacturing compressed tablets or capsules, however, the blending of several solid
ingredients is easier and more uniform if the ingredients are approximately the same size. It is more
difficult to create precise blends with trace ingredients (<1%) that are vastly dissimilar in size and
density. In some cases, this might require doing multiple key blends in a time-consuming and costly
process.

“We have to essentially achieve results within our blend uniformity requirements for every batch,
whether the formula is predominantly active ingredients and several excipient ingredients, or
predominantly excipient ingredients with very small amounts of active ingredient,” says Douglas Van
Pelt, Senior Director of Operations at Sigmapharm Laboratories LLC, a privately held specialty
pharmaceutical company based in Bensalem, PA that develops, manufactures and markets generic
and branded products in tablet and capsule form. “Homogeneity is very important because our
finished products are only as good as how well we blend them.”
“A typical blend uniformity specification of 90 percent to 110 percent with a standard deviation of not
more than five percent can be a challenge, but when you produce tablets with dosing as low as five
micrograms like we do, that is a much more difficult endeavor. We are consistently and successfully
doing that here,” Van Pelt adds.

Fortunately, with tumble blending equipment that is engineered to meet the requirements of the
application, the process can be simplified to rapidly produce a more precise, homogenous blend
containing necessary trace elements. Such blending can not only eliminate the need for key blends,
but also produce a better distribution of active ingredients.

Advancements in dryer technology can further improve quality and speed production, giving
pharmaceutical manufacturers even greater control over the process along with additional savings.

Limitations of traditional mixing equipment

Traditional equipment such as plow, ribbon, and paddle mixers, which use blades or paddles to push
material, face a number of challenges.

First, these mixers are limited to moving the material within the confines of their active area. The
mechanics force the material bed outward, leaving dead spots inside the vessel where material
moves more slowly or remains stationary.

Also, because these units are stationary, they have one stationary port at the bottom of the machine.
This port has a long neck, which isolates the material from any processing force during mixing.
Operators often need to empty the discharge area and manually reintroduce it back into the top of
the mixer. This means some portions of the mix will receive more additive than others. In fact, such
mixers typically cannot accommodate blends with seven percent or less of any one ingredient.
Another issue lies in the positioning of the intensifier bars or fluidization zones. These intensifier bars
should ideally be located in the mixing zone, where every particle passes through. Many times,
however, traditional mixers have their intensifier bars in dead zones. When this happens, the material
will not be fluidized properly, and active ingredients will not be incorporated throughout the batch.

Traditional mixers also tend to waste expensive additives. Because additives being
added to the vessel initially contact only a very small portion of the material, they get quickly absorbed
into the material bed. The typical response is to add more additives to achieve the desired mix
concentration, which drives up the cost.

Finally, because the pharmaceutical manufacturer is now wetting the material with higher quantities
of the additives, a longer drying stage is required to achieve the targeted results.

The benefits of tumble blending and vacuum tumble drying

To address the deficiencies of traditional mixers, a growing number of pharmaceutical manufacturers
utilize tumble blending. As a low-impact processing technique for handling sensitive or abrasive
solids, tumble blending is commonly used to create precise pharmaceutical blends that contain trace
ingredients (<1%) that are vastly dissimilar in size and density.

In contrast to traditional mixing, to eliminate dead spots, tumble blenders apply even turbulence in all
corners of the mix through a combination of macro and micro blending. This can eliminate the need
for key blends and produce a better distribution of active ingredients.

Macro blending is achieved by rotating the shaped vessel, allowing the material bed to fall away from
the vessel’s walls. Tumble blender vessel shapes are engineered to create a repeatable pattern in
which the entire bulk material moves to form a homogenous mixture. The blender moves at a precise
speed, with the vessel wall at a precise angle, so that the material cascades over itself. There is no
additional force from paddles, plows, or spiral ribbons – just gravity.
While this occurs, micro mixing (if needed) simultaneously proceeds via agitator blades located in the
mixing zone center of the vessel, where fine processing in the material transpires. This allows for a
gentle repeatable pattern that maintains a superior blending design while preserving the product’s
physical characteristics. Together, the macro and micro mixing evenly expose each particle to six
times more active blending per revolution than traditional mixers.

Because Sigmapharm’s Van Pelt had successfully used tumble blenders at a previous company, he
trusted their capabilities.

“At my previous employer, I made a product that had a narrow therapeutic range using a 30 cubic
foot tumble blender,” says Van Pelt, who notes that blend uniformity specification was a very stringent
95 percent to 105 percent, not a typical 90 percent to 110 percent. “The potency was 0.125 milligrams
inside a 125-milligram tablet, and we were able to achieve blend uniformity in 15 minutes, with good
repeatable results every time.”

The tumble blender was provided by GEMCO, a Middlesex, NJ-based manufacturer of tumble
blending and vacuum tumble drying equipment. According to Van Pelt, Sigmapharm has effectively
implemented a 30 cubic foot V blender and a one cubic foot slant cone blender from the tumble
blender manufacturer.

With the preciseness of the technology, a V-shape tumble blender is capable of achieving a standard
deviation of less than two percent, and a slant cone configuration can achieve a standard deviation
as low as 0.33 percent.
Van Pelt also appreciates the unique tumble blender loading option that provides an operational
advantage, compared to time consuming manual loading methods.

“The [tumble blender] lifts the drum containing the material to be blended against a gasket forming a
dust-tight seal,” he says.

According to Van Pelt, the tumble blender then rotates until the drum is inverted while opening the
discharge valve allows the contents to flow into the blender. The valve then shuts automatically and
the emptied drum returns to the loading position. The latest version allows for a pre-programmed
discharge sequence where the blender rotates back and forth several times in the discharge mode
to further ensure that the drum empties completely. “The entire operation is essentially dust free,” he
says.

In addition to tumble blending, a growing number of pharmaceutical manufacturers are finding that
vacuum tumble drying equipment offers significant advantages as well.

Most pharmaceutical powders for processing contain solvents or free radicals that need to be
removed to dry them effectively. Traditionally, to dry such powdered product, manufacturers use tray
dryers, where wet material is laid in thin layers on multiple racks of heated trays. However, this can
lead to uneven drying as heat is applied. Also, volatile material may be trapped on bottom layer
particles as a crust forms on the top layer of material. As the inner materials are insulated from the
inert atmospheric drying process, they remain unstable.

As a solution, advanced vacuum tumble drying equipment can resolve such issues and speed drying
while reducing cost. While typical tray drying relies solely on heat, vacuum tumble drying equipment
can utilize gas purging in addition to heat application.

In contrast to tray drying that essentially dries statically from the surface first and takes a long time to
affect the entire mass, dynamic vacuum tumble drying dries pharmaceutical powder energetically as
it rotates inside the vessel. This dries the powder faster, more evenly, with less labor, and is
particularly helpful in reducing residual organic solvents.

Protecting quality and the bottom line

Some pharmaceutical manufacturers may be inclined to use traditional blending and drying methods
because of their familiarity with such systems. However, those who take advantage of the superior
capabilities of tumble blending and vacuum tumble drying systems will protect product quality,
process control, and the bottom line to a degree not possible with traditional systems.
 Glossary
- Additives: substances contained in and part of the cosmetics, these have the
functions of conservation, color, aromas, among others.
- Capsule: Cylindrical or spherical wrapping of soluble material that is usually
formed by two pieces that fit with each other and within which a certain
medicine is placed.
- Homogeneous: It is formed by elements with common characteristics
referring to their class or nature, which allows to establish between them a
relationship of similarity and uniformity.
- Lot: set of similar or identical articles that are grouped together for a certain
purpose.
- Mixture material made up of two or more different substances which are
physically combined. A mixture is the physical combination of two or more
substances in which the identities are retained and are mixed in the form of
solutions, suspension and colloids.
- trace ingredients: any chemical element required by living organisms in
minimal quantities
- Tablet: Medication in pill form, usually flat and small in size, which is usually
taken without undone.
- Uniformity: Similarity or equality that present the characteristics of the
different elements of a set.

Source of consultation
https://www.pharmamanufacturing.com/articles/2019/optimizing-precision-
blending-of-tablets/
 OPTIMIZING PRECISION
BLENDING OF TABLETS

To meet stringent regulatory requirements, such as the United

States Pharmacopeia (USP), pharmaceutical manufacturers
require high-volume precision blending of formulations on
equipment that provides exceptional batch-to-batch
consistency and repeatable results.

When manufacturing compressed tablets or

capsules, however, the blending of several solid
ingredients is easier and more uniform if the
ingredients are approximately the same size.

Limitations of The benefits of tumble

traditional mixing blending and vacuum
equipment tumble drying

These mixers are As a low-impact processing technique

limited to moving the
material within the
confines of their active
area
for handling sensitive or abrasive solids,
tumble blending is commonly used to
create precise pharmaceutical blends
that contain trace ingredients (<1%) that
are vastly dissimilar in size and density.

Waste expensive
additives
Apply even turbulence
in all corners of the mix
through a combination
Vacuum drying of macro and micro
accelerates drying by blending.
reducing time and
costs, dries dust faster
and evenly