Originally Published PMPN July 2002
Pharmaceutical
Desiccants Boldly Going Where Moisture Hides
Desiccant selection shouldn't be an afterthought to package design.
by Jenevieve Blair Polin, Contributing Editor
Drug-formulation chemists who take the need for a catalyst or some other additive in stride sometimes consider the need for desiccants an affront, proof of their failure to create a robust, stable product. Desiccant selection may therefore be postponed until the end of product development, giving packaging engineers little time for thorough scientific determination of a product's precise needs. Such a situation may result in the failure to achieve the desired stability or may add unneeded packaging costs.
If you as a packaging professional are faced with this scenario, don't lose hope. Desiccant manufacturers can help you, through systematic engineering, determine the best fit for controlling moisture and oxygen, says Stefan Dick, PhD, product group manager for Süd-Chemie Performance Packaging (Belen, NM). "Industry advances in moisture and oxygen control are developing very quickly. We can act as consultants to help packagers specify the precise desiccant technology for specific applications. We advise customers on what combination of desiccants, humidity indicators, and other active packaging additives they should be using."
"I've seen a lot of mistakes out there," says Brad Wolk, president, Dry Pak Industries Inc. (Studio City, CA). "Generally, it's people using way too much desiccant rather than not using enough. Customers are often using two to three times what is required," he says.
Formulas are available, these experts point out, for determining the proper amount of desiccant for any application. The most relevant variables are the amount of void air space inside the package, the size of the package, and the desired shelf life. Careful analysis may result in cost savings.
"I may tell a customer, ‘Number one, you're in the wrong desiccant type. You should be using molecular sieve instead of silica gel, for instance. Number two, you need to improve your moisture barrier, because you are letting too much moisture in, and then you can use a smaller amount of desiccant,' " Wolk reveals. A better package, in this case, is one with a lower moisture vapor transmission rate (MVTR). "So by changing various elements of their packaging, companies can get the same shelf life or better and lower their overall packaging costs," Wolk summarizes.
Of bottled pharmaceutical and nutritional products, 65 to 70% have a desiccant, Wolk estimates. Manufacturers of products packaged in other formats are only now discovering the savings that desiccants may offer them.
POWDERED PRODUCTS
Many manufacturers of powdered products are starting to use desiccant inserts or caps, which suspend the desiccant on the underside of the roof of the cap. These suspended desiccants fill a niche for powdered products, in which the firm does not want a desiccant packet or canister to get lost.
Jean Woynicki, sales representative for Süd-Chemie, describes a custom solution for the manufacturer of a new drug, an antibiotic for pediatric use that is supplied as a powder for reconstitution. After filling the bottle with the powdered drug, the manufacturer inserts a custom-engineered desiccant stopper to plug the neck of the bottle. The desiccant stopper fits underneath the standard screw-on closure. When the pharmacist opens the bottle, he or she removes and discards the desiccant stopper. He or she then reconstitutes the product, creating a liquid, and recaps the bottle without the stopper for the consumer.
"Every bottle is different," says Woynicki, explaining that a custom-molded stopper is required. "The size and the material of the bottle determine the material that we would use to formulate the stopper. You have different dimensions and, in turn, different molds," she adds.
For years, Multisorb Technologies (Buffalo, NY) has provided large desiccant bags to antibiotic companies for intermediate storage of antibiotics after batch processing. The desiccant bags are put in drums, right with the antibiotics, which are stored for final packaging. Storage time may be as long as several weeks, so the potency of the antibiotics would degrade if too much moisture were present. "This sort of precaution has to be thought about ahead of time by engineers involved with manufacturing, most of whom do not have much experience in dealing with shelf stability issues," explains Multisorb's Richard Burke. "It can be a very expensive lesson to learn with a field failure of the pharmaceutical."
Süd-Chemie addresses the necessity for high desiccant visibility in large-volume
applications with food-grade desiccant bags in bright red plastic netting. These
may be placed directly in drums of powdered substances.
Wolk recently consulted with a company manufacturing a powdered nutritional weight-loss drink mix, storing it in big drums, and then running their packing line about once a week. Even in just a week, the drink mix began to clump because of the moisture in the air space at the top of the drum. They now insert large desiccant packs into the void air space in the drums, effectively keeping the drink mix dry until it is packed. "We were able to introduce desiccants as an intermediate step in the production process, as an internal safeguard to eliminate clumping and degradation of the product," says Wolk.
SHIPPING CARTONS
In the final packaging, this drink mix manufacturer is not using desiccants. The final package is a hermetically sealed can with almost no void air space, and the firm's shelf-life studies indicate no need for desiccants in the can. Protecting those cans from rust during worldwide shipping and storage, however, is another story. Many manufacturers are using large desiccant packs, such as Multisorb's TranSorb or Süd-Chemie's Container Dri II inside the shipping container to protect the final packaging from moisture. For instance, TranSorb bags can adsorb up to 200% of their 170-g weight in water. If not addressed, such moisture in the shipping container may cause not only rust, but also loss of labels or damage to printed cartons.
IN VITRO DIAGNOSTICS
Another trend is movement from silica gel to molecular sieve, especially in
the diagnostics industry. In the past year, more and more companies in the diagnostics
arena have switched over to molecular sieve because they are getting better
performance. Molecular sieve is the only desiccant capable of reducing humidity
to virtually zero relative humidity (RH). Silica gel and clay can achieve RH
of about 6%. Pregnancy and ovulation test kits, glucose test kits, or any tests
that use strips are good candidates.
Some IVDs are being marketed in injection-molded vials or housings that incorporate
desiccant-loaded films, a technology that is still evolving. The advantage of
incorporating the desiccant into the housing is the elimination of manufacturing
steps. The manufacturer can eliminate their desiccant-dispensing equipment from
the production line. Desiccant in the housing also eliminates the possibility
that someone will ingest the desiccant as well as the possibility of desiccant
contaminating the product if the packet or canister is accidentally opened.
Desiccant tablets inserted in the injection-molded housing of a single-use
IVD, such as the wand of a home-use pregnancy test, are also invisible to the
consumer. Because they are solid, they are unlikely to contaminate the test.
Süd-Chemie bevels the edges of its Tri-Sorb molecular-sieve tablets designed
for this application to reduce chipping of the tablet and jamming of insertion
equipment.
"I've had some clients consider desiccant-loaded films in the housing, but when they looked at the cost of doing that versus just putting in a small packet, a low-profile packet, they decided to go with the packet," Wolk says. "The packets are much more readily available, and the plastic housing with the desiccant is still a work in process."
EFFERVESCENT TABLETS
CSP Technologies Inc. (Auburn, AL) is the leader in desiccant-loaded film.
It has developed an engineered-polymer technology, adding desiccant or other
active components to any base polymer (polypropylene or polyethylene) to create
a desiccating polymer film. With a two-shot molding process, it creates an "active"
container, in most cases a flip-top vial, that has an integral active liner
incorporated seamlessly and permanently into the primary package. That active
component can be merely a desiccant liner or it can serve more than one function.
CSP is currently working on an application for a pharmaceutical company to remove
the unpleasant odor of a pharmaceutical sulfur compound emanating from an effervescent
tablet. "We not only protect it from moisture, but also scavenge the malodor,"
says Billy Abrams, vice president, business development, for CSP.
In the next 12 to 24 months, many pharmaceutical and nutritional products will
be hitting the market in CSP packages. An effervescent tablet will be marketed
in the United States in 2003 in CSP's two-shot vials with integral desiccated
liners. CSP is also working with companies commercializing nutritional effervescent
tablets to be packaged in these vials for distribution in Europe. In September
2001, CSP opened a plant in Niederbraun, France, to meet European demand.
"Once you go through stability, you still have the automation hurdle to get over as well," Abrams says, commenting on the time line. "Fortunately, we have already designed, engineered, and installed high-speed automation for packaging effervescent tablets into our flip-top vials." CSP worked with automation partners (tablet-filler company Soehnel and a cartoner company, Promatic) to engineer automation equipment that accommodates the two-shot flip-top vial.
A DESICCANT ALTERNATIVE?
Adrian Possumato, technical sales representative for the Northeast and Puerto
Rico for Multisorb Technologies, explains why Multisorb sees an opportunity
for a completely different approach to achieving stability in pharmaceuticals
and nutritionals.
"In many cases, the real problem in drug instability is oxidation, not
moisture, per se," Possumato says. Moisture serves as a catalyst for oxidation
in the presence of oxygen. For years, the industry has been using the control
of moisture through desiccant use as a roundabout way to prevent oxidation.
Multisorb is working with makers of solid-oral-dosage hormonal products (contraceptives
and hormone replacement therapy products) who are using Multisorb's FreshPax
or FreshPax/Pharma oxygen-absorbing packets to "go after the end point,
taking the oxygen out of the package," says Possumato. "If there is
no oxygen, there is no problem. Unless your product is susceptible to hydrolysis,
any moisture content is really moot," he adds. The FreshPax packets are
formulated for standard HDPE bottles for pharmaceutical packaging.
This alternative may soften the drug-formulation chemists' view of desiccants and their like. "This option gives new life to products that could not be stabilized in the R&D lab," says Possumato. "If they could not be stabilized, they could never be commercialized. Now packaging changes may make these products viable," he predicts.
Image of TranSorb Desiccant for Shipping Containers Courtesy Multisorb Technologies
Copyright ©2002 Pharmaceutical & Medical Packaging News
