When it comes to the production of soft-gelatin capsules, a technology that has been around for more than 80 years, it is still a unique process that can require tight control and a bit of finesse.
“There’s a lot of science involved, but if you talk to any operator who has been around the industry for a length of time, they say it’s about 40 percent science and 60 percent black magic,” said Charles St. Louis, Owner of St. Louis Soft Gel Consulting & Sales.
“The reason is that you’re dealing with natural substances most of the time, like your gelatin—it comes from skin, bone marrow, pork skin, or some blend of natural substances,” he explained. “Even though you get a C of A [Certificate of Analysis] that says it’s all the same, it reacts differently.”
Mirror on the Past
While the production formulas may require some tweaking, the design and concept closely mirrors the original process, somewhat unusual at a time when new technology has changed the way so much of manufacturing takes place today.
“The technology for it is all the same,” said St. Louis. “When you look at the equipment, it’s the same as the first machine. The dies are upfront. There are two rotary dies, a segment that sits in the middle of it, a displacement pump on top that pushes the medicine through the lines.”
The primary advancements over the years have involved the addition of technology to speed the process—PLCs, controllers, tech screens, operations, and the size of the rotary dies used—all improvements that can produce in an hour what may have taken a full day to accomplish in the distant past.
Roots of Encapsulation
It all started back in 1930 when Robert Pauli Scherer, a 24-year-old chemical engineer, envisioned a way to produce easy-to-swallow soft gelatin capsules in a form/fill/seal encapsulation that also protects ingredients from tampering.
Working in his parent’s Detroit basement, the young entrepreneur designed the rotary die encapsulation process and in three years brought it to market. The rest is pharmaceutical history.
It is a process that is heavily dependent upon accurate control of temperature and humidity, along with a precise application of airflow dehumidification.
A softgel consists of a gelatin-based shell surrounding a liquid fill. The shells are a combination of gelatin, water, opacifier, and a plasticizer, such as glycerin or sorbitol. In the encapsulation process, two flat ribbons are manufactured and brought together on a twin set of rotating dies.
The dies contain recesses that cut out the ribbons into a two-dimensional shape and a seal is formed. A pump delivers a precise dose of fill material through a nozzle, and a heating process facilitates the sealing. The flat ribbons expand into a three-dimensional product and then are put through a drying process.
The wedge is heated to facilitate the sealing process. An injection causes the two flat ribbons to expand into the die pockets, giving rise to the three-dimensional finished product. After encapsulation, the softgels are dried.
In very simple terms, it involves spreading warm, liquid gelatin over a stainless steel drum with cool dry air applied as the drum rotates. The resulting soft capsules are filled with ingredients, transferred into trays, and then subjected to a drying process to remove excess moisture and produce a specific capsule hardness.
Temperature, Humidity, and Drying
The ideal temperature range in the encapsulation area generally is estimated to be around 70° to 75° F with a relative humidity (RH) of 30 to 35 percent. The drying tunnels can be drier, usually 75° with 20 percent RH.
There are three different methods that can be used to cool and dry the air for the encapsulation unit and drying tunnels: liquid desiccants, dry desiccants, and conventional refrigeration, according to Mark Piegay, Northeast Regional Sales Manager, Kathabar Dehumidification Systems (Alfa Laval).
“I wouldn’t say too many people use a conventional refrigeration approach,” he said referring to use in encapsulation areas and drying tunnels, adding that such an approach wouldn’t be suitable for an application that requires 30 or 20 percent RH.
“Then that leads you to the use of desiccants,” he said. “Now my decision is: do I use dry desiccants or liquid desiccants? I would say there are many companies that use both. We manufacture both technologies, but for this particular application we like to use liquid desiccants.”
The dry desiccant system uses a wheel impregnated with gel, but there are oils in the airstream and glycerin from the process could start to cake up on the wheel. The dry systems also tend to be less energy efficient when used in this area.
“Your downtime is going to be a lot less with the liquid system because you don’t have to worry about that oil in the air,” Piegay said. “A [dry] desiccant wheel isn’t going to clean the air for you, a liquid desiccant can do that. In the pharmaceutical industry it’s great to have that benefit of being able to prevent bacteria growth. Anything that was in the air stream—dust and dirt, bacteria and viruses—is going to get killed or scrubbed out via the liquid desiccant.
“With liquid desiccant you really don’t have to do anything to it to maintain its ability to kill bacteria and viruses because the desiccant itself has infinite life expectancy,” he added. “If the bacteria or virus in the air gets into the liquid desiccant, it gets killed pretty much in a second.”
Beyond that, a filtering system is used to filter any dust or dirt out of the solution.
To streamline the process, instead of returning air right back to the desiccant dehumidification system, it could be cooled and redistributed to certain areas, such as for inspection and capsule printing, or possibly in some packaging areas.
“You don’t have to do any dehumidification with it since that air already is very dry,” Piegay said. “It’s kind of a cascading effect.”
Other advantages in using liquid desiccant involve automation, controllability to +-1 percent RH, and adaptability to a changing environment—for example quickly adjusting to changing temperatures and RH swings.
“When it’s really humid one day and dry the next, the liquid system has ability to adapt to those conditions,” he said.
As for typical savings in using a liquid desiccant system, Piegay said it varies.
“Compared to dry systems, we’ve seen savings of 20 to 30 percent using a liquid system depending on the setup,” he said, indicating that sometimes use of a dry system can be more efficient.
“If it’s a warm dry application then more than likely your dry desiccant system will be favorable for energy,” he said. “But if it’s a cool dry, like 70 degrees/30 percent RH, there’s a good chance you can see the energy savings of 20 to 30 percent.”
Since Kathabar markets both liquid and dry desiccant systems, the company puts together an economic value comparison between the two, but leaves it up to the potential user to decide which one makes more sense, unless oil on a wheel is an issue, he said.
With increased awareness of energy costs, companies today evaluate the total cost to own and operate equipment, rather than initial cost alone. A typical evaluation takes into consideration the first cost, installation cost, and operating costs for dry and liquid desiccant dehumidification systems.
The cost for various systems is calculated and a value comparison based on specific local weather data, actual energy costs and system operating schedule is presented, along with a comparison to conventional refrigeration systems.
While the basic concept of the rotary die encapsulation process has not changed in more than 80 years, some companies are exploring new technology involving continuous dryers.
“If you can take a product, put it into the inspection line, and send it into a bottle right after that, that’s a continuous manufacturing,” St. Louis said. “If you’re used to taking product into a tunnel or into a room and let it sit there for 48 to 72 hours, then money’s just sitting there.”
In the meantime, to speed the process, some companies are putting additional dryer baskets together in the line, he said. For example, if one typically used six or eight baskets, they might go up to 10, 12, 14, or 16 baskets, and bring down the RH to 20 percent from 30 percent.
Some new technology may be just around the corner for the U.S. market. St. Louis pointed out that a patented system developed in Japan places air directly from the system into the dryer, actually reducing the number of baskets while actually improving and speeding the overall process.
Available right now only in Asia, St. Louis said he is working to bring the technology to U.S. customers. He estimated time savings through the process might bring work that now takes two to three days down to handling it all in a single day.
This article can also be found in the INTERPHEX 2016 Show Daily: Thursday, April 28.
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