Heading Off Moisture

The Multiform CSF Container/Closure System developed by Multisorb and Neutroplast Industria bars moisture ingress while processing tablet moisture.

Newer desiccant technology applications address shelf life requirements, patient safety concerns, and filling line efficiency.

High-capacity desiccant solutions, such as in-wall desiccating polymers or compressed desiccant technology, tackle free moisture in packaging of highly sensitive rapid-dissolve and extended­release products. Improvements in traditional drop-in technology promise production cost savings.

Multisorb Technologies (Buffalo, NY) has doubled, and plans to triple, manufacturing capacity for its recently redesigned SorbiCap canister format, which is used for moisture management systems and its StabilOx oxygen and moisture scavenging canisters.

“While we are seeing most of the increasing demand for desiccants going to packets, some of our larger customers have made purchasing decisions on canister dispensing equipment and want to see some return on those assets,” says Adrian Possumato, global director, healthcare packaging.

The SorbiCap canisters feature radius edges that support increased speeds on legacy dispensing equipment, in addition to offering an elegant look. The SorbiCap is a one-piece system that doesn’t come apart during dispensing, as two-piece canisters can, Possumato says.

Vibration-welded porous polyethylene ends prevent dusting from sorbent material particles. “Dusting is most noticable when iron powder is used for oxygen absorption in canisters with screen closures. We call it the pepper shaker effect,” he adds.

As alternatives to traditional loose-fill desiccants, new formats are often designed to increase the level of moisture management. Molded desiccant infused polymers have emerged as replacements for the canisters and packets.

For product requiring high moisture and oxygen protection, Alcan Global Pharmaceutical Packaging (Montreal) has launched the StabilitySolutions line of plastic bottles that situate sorbent materials within bottle layers. Co-extruded blow-molded bottles in the patent-pending technology maintain dry and/or oxygen-free head space, replacing the need for a drop-in desiccant or other scavengers.

Multilayer Bottles

StabilitySolutions DRY incorporates a calcium oxide (CaO) desiccant in the product contact layer of a bilayer HDPE structure. CaO reacts with moisture to form calcium hydroxide (CaOH₂) in a nonreversible chemical reaction. Oxygen barrier is provided with the StabilitySolutions Barrier bottle, in which an ethylene vinyl alcohol (EVOH) layer is sandwiched between two layers of HDPE.

“This is a first-of-its-kind pharmaceutical solution using standard coextrusion blow-molding technology,” says Larry Blake, director of marketing, Alcan Pharmaceutical Packaging—Plastics Americas (Pennsauken, NJ). “With the bottle acting as a desiccating container, we are always ensuring the product remains in its most stable and comfortable state.”

Blake says the technology provides a total delivered cost that is competitive with drop-in desiccants and offers a cost-effective alternative to cold-form and other high-barrier blister packaging. By using a desiccating bottle, customers can simplify their filling lines and avoid desiccant costs and control and containment requirements. “There is no opportunity for product contamination, the patient cannot discard the desiccant, and you are eliminating a potential choking hazard since there is no foreign body in the bottle.”

Thicknesses of CaO and EVOH layers and HDPE structural layers can be varied for different barrier and bottle structure requirements. Blake says the two systems can be combined, adding a CaO/HDPE interior desiccant layer to the barrier bottle construction. “We select the correct mold and customize the extrusion systems to arrive at the container volume necessary,” he says.

Figure 1. Open containers with different weights of calcium oxide desiccant incorporated into the product contact layer absorb moisture for extended periods, in Alcan Packaging�s coextruded blow-molded desiccant bottle solution. (click image to enlarge)

Alcan testing demonstrated that the drying action of StabilitySolutions DRY through multiple bottle openings and closings is repeatable, ensuring extended product shelf life. In a simulation of real-life usage, containers stored in 92°F and 85% RH conditions were opened for one minute and resealed. Reclosed bottles regained low relative humidity to the range of 31⁄5 to 5% for 10 bottles tested.

In a second test using 120°F and 50% RH to measure the terminal moisture-absorbing capacity of open containers, 5-gram CaO bottles averaged continuous weight gain to over 2 grams beyond 200 days.
TricorBraun (St. Louis) recently completed regulatory approval and ramped up sample production of bottles incorporating the DryKeep desiccant polymer compound. TricorBraun is the exclusive licensee in the United States for DryKeep, which employs a natural salt desiccant manufactured by Sasaki Chemical (Japan).

Drug Master Files on the compound and component materials have been filed with FDA. Containers incorporating DryKeep have recently gained U.S. Pharmacopeia 661 and 671 certification.

TricorBraun is working with two converters that are producing bottles for the commercially-ready solution, says Drew Williams, vice president, strategic markets.

“In-wall desiccants are the new frontier,” Williams adds. “People want to eliminate the physical desiccant in the bottle and require higher moisture capacity desiccant solutions to extend shelf life and for product shipped to extreme climates.”

High-Capacity Action

DryKeep molecules are encapsulated in an HDPE layer for coextrusion blow molding of multilayer bottles.

“DryKeep absorbs water through the form of a hydrate returning to its natural state,” says Jad Darsey, sales manager for strategic markets, TricorBraun. “This absorption occurs without the chemical reaction that creates a high pH when calcium oxide is used.”

The system is hydrated without increasing molecule volume, which can lead to swelling of the desiccant layer, delamination, and aesthetic issues, Darsey adds. DryKeep absorbs 100% of its weight in water, providing three times more moisture capacity per unit weight than calcium oxide. In addition, “the moisture uptake is slow and controllable, so containers don’t require special care in the filling process to ensure their moisture capacity is intact. The measured absorption allows formulating bottles to maintain specific internal RH environments,” Darsey adds.

Sanner Plastics Technology is launching container systems with molded desiccant pieces for test strips. In the Easy Lift system, test strips are packaged in a basket integrated in a bottle. Strips are raised above the bottle lip for easy withdrawal when the cap is opened. Sanner is also offering a molded test strip dispenser, incorporating a molded desiccant polymer cartridge.

“The Easy Lift solution promotes easy withdrawal of the strips in a bottle format known to consumers. With the test strip dispenser, individually dispensed strips are protected from damage and microbial contamination, with a high level of moisture control through the desiccant cartridge,” says Michael Ross, business development manager, Sanner of America, Inc. (Marlton, NJ).

Multisorb offers its Multiform Coated Solid Form (CSF) sorbents for increasing functional moisture management per unit volume of desiccant in in vitro diagnostic devices. The Multiform CSF also provides a high performance solution in desiccant bottle cap applications.

Where drugs are supplied in pass-through trade sizes, as is often the case in Europe, the need for secondary stability profiles on repackaged product is often avoided. But trade-size bottle packaging presents challenges when foil seals can’t be used.

“The foil seal is a very effective static barrier for blocking moisture ingress, but many countries forbid the use of desiccants in direct contact with the drug product,” Possumato says. “We have seen up to an eightfold increase in moisture ingress through the cap and bottle joint when you eliminate the foil seal.”

Multisorb has partnered with Neutroplast Industria de Embalagens Plasticas, SA, (Portugal) to offer a closure system that provides an active barrier against moisture ingress, while simultaneously attacking free moisture in the tablets.

Fitted into Neutroplast’s screw closure, Multisorb’s Multiform CSF desiccant, a compact silica gel desiccant based on condensed density technology, features twice the absorbent capacity of a similar-sized loose-fill desiccant.

“The customer was not achieving their stability requirements with the loose-fill desiccant cap system they were using,” Possumato says. “With lower-capacity desiccant solutions, the free moisture in the tablets compromises the desiccant’s active barrier function.

“With the Multiform CSF system, we have twice the capacity of desiccant per unit volume in the closure for more blocking power of free moisture over time,” he adds. “And we are effectively performing a final manufacturing step by processing all of the free moisture out of the tablets in their commercial packaging.

“For many drug products, a reduction in tablet free moisture results in decreased molecular mobility and a reduced rate of chemical degradation,” Possumato adds.

The Flow-Limiter from Süd-Chemie Performance Packaging (Belen, NM) uses the company’s Advanced Desiccant Polymer for moisture control in bottle packaging. Featuring slots that control pill dispensing, the device is secured in the cap below the induction seal, allowing the seal to be retained.

“The Flow-Limiter is being tested by several customers, and we have continued to work with customers on various flow-limiting and desiccant component combinations,” says Mark Florez, global marketing manager, Süd-Chemie Inc., Performance Packaging.

Süd-Chemie Performance Packaging is establishing its first production facility in China, where it has operated a sales office in Shanghai for several years. Operations at the facility in Changshu, 120 km from Shanghai, will include designing, molding, filling, printing, assembly, and distribution of its polymer and desiccant packaging solutions. The FDA and CGMP-compliant cleanroom manufacturing facility will open later this year, says Florez.

Expansion of healthcare throughout China, as the population ages and urban population growth accelerates, will grow the Chinese drug market by 20 to 25% per year over the next five years, Florez predicts.

“China is expected to become the fifth largest drug market in the world by 2010,” he adds. “Another sign of China’s significance is FDA’s move to establish a permanent office in the country to allow greater access for inspections and interaction with manufacturers shipping to the United States.”