Granulation is one of most important unit operations involved in solid dosage form manufacturing and several granulation technologies
have been developed. Traditionally, an aqueous solution of a binder is sprayed on the powder during mixing in a granulator.
In 2003, The Dow Chemical Company (Midland, MI) introduced foam technology for delivering aqueous binder systems in high-shear
and fluid-bed wet granulation applications (1) (see Figure 1). A foam generator can be set up with a binder solution tank
and high-sheer granulator to introduce the binder as a foam rather than spraying or pouring in binder onto a moving powder
bed. Last year, Pharmaceutical Technology published an article discussing the scale-up of foam granulation technology in a high-shear process (2) (see Figures 2, 3).
As a follow-up to that discussion, Paul Sheskey, research and development leader at Dow, provides an update on foam granulation,
including process challenges the company has encountered from industry and future applications of the technology.
Q. What was the motivation to develop a new granulation technology versus conventional granulation techniques?
A: We became aware of the granulation needs of the industry through the sale of our functional polymers, whether it was for
granulating a matrix controlled-release system using METHOCEL cellulose ethers polymers or immediate-release granulation using
our low molecular-weight polymer family. A significant issue experienced throughout the industry, as represented by a large
number of research papers published throughout the years, is the uniform distribution of the liquid/binder combination evenly
throughout a moving powder bed. It may appear to be uniform when spraying, but it doesn't always happen. We've referenced
papers by Litster and Hapgood that showed this is not a very easy thing to accomplish. In their studies they proved it at
the very basic level.
Manufacturers of pharmaceutical granulations would call us saying that they were having trouble either during their formulation
development work or in a production setting. We determined that a significant proportion of their issues directly related
to the even distribution of the granulating liquid. They have hydrophilic polymers in their formulations that tend to preferentially
grab the water in the granulating liquid and sometimes this would interfere with its uniform distribution. So we investigated
various atomizing techniques when spraying the binder solutions. We did a lot of work to better understand the issues so that
we could provide the pharmaceutical formulators specific, hands-on type of advice. However, even that was not doing as good
a job as was needed for the pharmaceutical industry. Then we discovered foam technology for granulation applications in our
laboratory. My colleague and co-inventor, Colin Keary has a lot of expertise in the area of foams when he was a scientist
in the oil well industry. Working in combination, we serendipitously came up with this for pharmaceutical granulating. That
satisfied the need of evenly distributing the liquid binder phase much better than a spray could do. That is a recognized
need of the industry and that is what foam helps with tremendously.
Q. What are some of the unique challenges and applications of using foam granulation?
A: The pharmaceutical industry is very conservative when it comes to new applications and new technologies. Our job has been
to educate people on the use of this technology globally. This has become better, but it always takes time. We've seen that
once it gets into a company, they'll also use it for the everyday-type granulations.