To Gel or Not to Gel?

Director of Sales and Marketing

EMBOCAPS®

For more than a century, empty hard capsules have been a safe, effective dosage delivery system. However, half a century in, recognizing that although gelatin was ideal for hard capsules, it was not perfect, a large pharmaceutical company patented a hard capsule manufacturing process using a modified water-soluble form of plant-derived cellulose. At the time, in an industry completely based on the performance and characteristics of gelatin hard capsules, the challenges of this new “veggie” capsule outweighed the benefits. It was shelved. Fast forward to the late 1980s/early 1990s when the capsule industry was irreversibly altered by three letters: BSE. Bovine spongiform encephalopathy or “Mad Cow Disease” rocked the gelatin world.

Seemingly overnight, countries put up walls banning the importation of bovine-derived gelatin products based on regions/risks and the BSE paperwork headache mountain was born. In the 1990s, the industry was abuzz with a new term—”Veggie Cap” or more specifically Vegicaps®, a term still used to describe all vegetable capsules, despite their brand (similar to Kleenex® and facial tissue). Manufactured using pure Hydroxypropyl methylcellulose (aka HPMC and/or Hypromellose) these new capsules were poised to revolutionize the capsule industry. But despite the marketing fervor, a long road to gelatin equality lay ahead. 

HPMC has many of the required characteristics to replace gelatin in hard capsules. But, it lacked one key characteristic; HPMC, while an excellent film former, was a poor gelling agent. A pure HPMC solution used on a traditional hard gelatin capsule production machine (HCM) will not produce capsules. 

There are only two choices: change the machine or change the raw material. In the early 1990s, I was offered a job at the original “vegicaps'' manufacturer. This company modified a capsule-making machine to match the HPMC raw material. Horror is the right word to describe my very first glimpse. The sight of two old mechanical capsule machines—sliced and diced into an almost unrecognizable configuration with dumbbell weights hanging from the upper decks and suspension springs forcing the mechanical movements to keep time—was scary. 

Hampered by the extreme heat required to force the liquid HPMC raw material to rapidly increase viscosity (i.e. thermogel), these machines clearly voiced their displeasure through the slamming of hot metal against hot metal and groans of unhappy cam followers. Needless to say, I declined the job opportunity.

 It was a gelatin capsule world at the time, but the race was on. If you wanted a seat at the adult table, capsule producers needed a commercial cellulose option. Most major brands, including the market leader at the time, opted for the path of least resistance— modify the raw material and use existing production machinery. A vegetable capsule using HPMC and carrageenan, the gelling agent of choice, was quickly developed and patented, other veggie caps using gellan gum, pectin and other non-animal gelling systems blended with the HPMC were also quickly developed.

By the mid- to late-1990s, most capsule manufacturers offered a non-animal option. The problem was, they were not very good. The entire empty hard capsule customer base had equipment, fill material formulations and processes rooted in and designed for gelatin capsules. One veteran encapsulation technician in the late 1990s told me running veggie caps in a filling machine “is like taking a rowboat on the freeway to get to work”. 

This industry feedback forced both capsule manufacturers and encapsulation equipment companies to improve their products. 

Special tooling became available for filling equipment specifically designed for vegetable capsules and capsule manufactures refined their processes. By the early 2000s, veggie caps were better, but nowhere near equivalent, to gelatin capsules. 

Progress to improve them was hindered by the delicate dance required by capsule manufactures to circumvent patents. After 10 years of minimal improvements in vegetable capsule performance, a realization and homage to gelatin capsules began taking hold. What if…similar to gelatin capsules where there are multiple varieties based on end use (i.e. Blended, 100% Bovine, 100% Porcine, 100% Fish gelatin capsules), what if… there is not one perfect veggie cap? 

Capsule manufacturers revisited the two options of manufacture. 1. The Thermogel method, where the capsule-making machine is modified to utilize pure HPMC and 2. The Gelling Agentassisted method, where the HPMC solution is modified to run on a traditional capsule manufacturing machine. 

Armed with the idea that maybe there is not a “one-size fits all” HPMC capsule and now unencumbered due to the sunset of most of the HPMC capsule patents, most major brands today offer both Thermogel and Gelling Agent-Assisted-versions of HPMC capsules with carrageenan the gelling agent of choice. 

Present day, over 30 years since the original HPMC capsule was introduced, HPMC capsules are much improved. They are chemically inert, crystal clear, have low water activity and are much more resilient to temperature and humidity extremes compared to gelatin capsules. Lifestyle choices, religious restrictions, ease of exporting/ importing in the global marketplace and sustainability concerns now favor HPMC capsules over gelatin capsules. 

Eventually the capsule market will come full circle, where HPMC capsules are the dominant capsule delivery system and gelatin capsules are for niche products only. Our children and grandchildren will turn their noses up at the idea of a capsule that you put in your mouth is made from animal skin and bones…yuck!

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