Locked and Loaded

Two-piece hard-shell capsules are versatile. They can hold liquids. They can hold pastes. They can even hold powders. But within that versatility lies a potential complication: They are prone to leak.

“Any two-piece capsule that does not contain a seal has a high likelihood of leakage,” says Shannon Putnam, manager of equipment business at Qualicaps Inc. (Whitsett, NC), which manufactures capsules and capsule-sealing equipment. “Sealing is highly recommended for ingredients with viscosities between 100 and 1000 cP.”

According to Dennis Phillips, technical service representative for the company’s equipment division, capsule sealing helps solve several problems at once. First, it offers protection by providing a visual tamper-evident seal. Second, it achieves stability by preventing leaks. Third, it enhances the visual appeal of capsules by adding additional color options. These kinds of benefits make hard-shell capsules an attractive choice for many dietary supplement and drug manufacturers.

TWO-PIECE CAPSULES: A BRIEF HISTORY

Hard-shell capsules and liquid ingredients have had a long and complicated history spanning over 150 years. In 1834, the inventor of the first modern capsule injected a liquid into a bubble of dried gelatin. Twelve years later, another inventor created the first two-piece hard-shell capsule, which was also intended to deliver liquids and pastes. The tablet, designed for solid ingredients, followed about 60 years later.

According to Brian Jones, scientific adviser to Qualicaps, liquid filling of hard capsules started to fall out of favor in the early 1900s, about the same time that tablets appeared, in part because the capsules were not self-locking and tended to leak oily materials. Liquid filling also began to take a back seat to solid dosage forms, which became more popular with the rise of antibiotics in the 1930s.

By the 1960s, however, the situation changed again. Eli Lily & Co. (Indianapolis) introduced self-locking hard-shell capsules, and equipment manufacturers subsequently identified ways to prevent leakage by sealing capsules with bands of gelatin and hypromellose (HPMC). While today the tablet remains one of the most widely used dosage forms, capsules are seen as an effective delivery system for many applications.

CAPSULE-SEALING BENEFITS

Capsule sealing may offer several benefits. One is that it can indicate product tampering. While tampering is rare, it is still a concern for manufacturers. FDA requires tamper-evident characteristics for certain kinds of over-the-counter drugs (Compliance Policy Guide, sec. 450.500), and while it’s not necessarily required, some dietary supplement manufacturers abide by drug good manufacturing practices (GMPs) in lieu of the final supplement GMPs. Sealing bands can also help achieve compliance in placebo-controlled trials by preventing the subjects from opening the capsules to guess their contents. “A visual tamper-evident seal for two-piece capsules provides both the manufacturer and the consumer complete confidence that the product has not been altered,” Putnam says.

Another advantage is that it stops leakage. Sealing bands preserve product potency by creating a hermetic barrier that prevents internal liquids and odors from leaving the capsule and external gases from entering. According to Matthew Schappert, business development manager for the capsule division at Qualicaps, 98% of the gas vapors that enter capsules do so through a gap in the overlap area between the cap and the body. Research also shows that there is a 60-fold reduction in the amount of diffusing oxygen that passes through the cap and body in band-sealed, locking capsules compared with regular capsules.

A third benefit of capsule sealing is that it helps create brand identity through the use of color. Brightly colored sealing bands can add a third tint to two-piece capsules, says Putnam, rendering them more appealing to consumers and making them more difficult for competitors to imitate. Several major drugs, such as Astra-Zeneca’s (Wilmington, DE) Nexium, for instance, use color (e.g., “the purple pill”) as part of a marketing campaign.

CAPSULE-SEALING EQUIPMENT

Several product-tampering scares helped prompt the development of high-speed capsule-sealing technology in the 1980s. Modern sealing systems now band tens of thousands of capsules per hour. The Qualicaps Hicapseal 40, for instance, bands up to 40,000 capsules per hour, while the Hicapseal 100 bands up to 100,000. To assist with product development efforts, Schaefer Technologies Inc. (Indianapolis) also manufactures a lab-scale bander that simulates the Hicapseal process, banding up to 100 capsules per hour.

Automatic sealers use a variety of processes to transport and band capsules without denting or damaging delicate surfaces. In the Hicapseal, capsules flow from the hopper into a three-drum rectification system, where they are gently oriented in the proper direction. The capsules then move into sealing slats, where they rotate until they are precisely situated. As the capsules travel across a conveyor belt, a sealing disk transfers heated sealing solution onto the capsules. A second disk corrects irregularities and unevenness by eliminating air bubbles, trimming the band, and adding additional solution.

Capsule Inspections Lead to Improved Results

Does the quality of empty capsule shells influence the quality of finished capsule products? Yes, according to one major contract manufacturer.

Recent data from Nutritional Laboratories International’s (NLI; Missoula, MT) 100% inspection process program found that the condition of empty capsule shells was directly related to the condition of capsules that come off of the company’s encapsulation machines.

“The 100% inspection process was a visual inspection where NLI inspectors evaluated product on a conveyor system to detect physical defects like split or unlocked capsules, or dented ends,” explains Ned Becker, NLI’s vice president of sales, marketing, and business development. He adds that NLI also gathered information from an in-process random sampling and inspection system that tracks key physical attributes on a real-time basis.

NLI saw improvements in overall encapsulation output and efficiency after sharing the data with its capsule vendor. “Feedback on an empty-shell lot-by-lot basis allowed them to better understand their own manufacturing process and is resulting in improved, more-consistent capsules,” Becker says.

The bands are composed of gelatin or HPMC, depending on the type of capsules being banded. “It’s important to note that we are applying the same gelatin to the capsules that the capsules themselves are manufactured from and are not adding anything to the product,” says Phillips. “Since this is the same material, it creates a very good bond with the original capsule wall. The same is true for the HPMC sealing solution.”

After applying the sealing solution, the system transfers the capsules to a drying cabinet. There, filtered ambient air blows onto the wet bands without stripping away moisture, thus preventing brittle capsules.

IN CONCLUSION

Automatic capsule sealing can reduce the potential for leakage, product tampering, and consumer confusion, ensuring that products deliver what they promise. It can also add marketing appeal to capsules. While sealing bands may not be necessary for all types of products, many kinds of supplements, liquid and solid, can benefit from their contributions.