• October 24, 2020

Disruptive Science

Credit: TTI

A new version of synthetic nicotine eliminates the cancer-causing impurities in leaf-derived nicotine.

By Timothy S. Donahue

No tobacco-specific nitrosamines (TSNAs). A new synthetic nicotine coming to market has none of the possible cancer-causing impurities that are found in traditional leaf-derived nicotine. In November, eLiquiTech, a wholly owned subsidiary of Tobacco Technology Inc. (TTI), will release its newly patented SyNic synthetic (S)-nicotine. The announcement has the potential to revolutionize next-generation tobacco products, such as electronic nicotine-delivery systems (ENDS), oral nicotine-delivery systems and heat-not-burn (HnB) products.

SyNic USP/EP, SyNic nicotine bitartrate and SyNic polacrilex resin are manufactured in U.S. Food and Drug Administration (FDA)-registered facilities using current good manufacturing practices (cGMP). These products have confirmed purity levels of more than 99.9 percent, (S) levels of more than 99.7 percent and are free of TSNAs and carcinogens, according to eLiquiTech CEO George Cassels-Smith. “What is the value of noncarcinogenic nicotine base to any tobacco product manufacturer?” he asks. “What is a noncarcinogenic tobacco product portfolio worth to the tobacco consuming public? But high-purity, pedigreed natural nicotine will continue to have a large seat at the table nevertheless.”

SyNic got its start seven years ago when e-LiquiTech began working with U.K.-based Zanoprima Lifesciences with the goal of developing a unique and patented portfolio of synthetic nicotine products. The group wanted those products to cover the entire nicotine value chain with a focus on next-generation tobacco products.

E-LiquiTech, through TTI, is committed to Zanoprima to serve as SyNic’s global distributor and the manufacturer of record for synthetic nicotine bitartrate and synthetic nicotine polacrilex resin as well as proprietary SyNic e-liquid formulas. “Ensuring that synthetic nicotine is readily available is the right thing to do for our industry—and now also is the right time to do it,” said Cassels-Smith.

Zanoprima holds the patent and eLiquiTech maintains the exclusive rights for global distribution to the tobacco and ENDS industries, but the product won’t be available to everyone, according to Cassels-Smith.

“This will not be available directly to the consumer market. We will soon post a set of standards online that manufacturers must meet to purchase our synthetic nicotine,” he says. “This product is not intended to circumvent the rules governing the tobacco and ENDS industries nor evade regulation. We will not sell it to companies that have that intent.”

SyNic will refrain from entering the highly contentious U.S. vapor market until its potential customers can show they have an accepted for review premarket tobacco product application (PMTA) submitted to the FDA’s Center for Tobacco Products. “Our objective is to work with the FDA, not around it,” says Cassels-Smith.

When synthetic nicotine first appeared on the market in 2016, the product was marketed as being a potential way to circumvent the FDA’s proposed deeming rule for next-generation tobacco products. The FDA’s definition of “tobacco product” includes any product made or derived from tobacco, including any component, part or accessory of a tobacco product. E-liquids that do not contain nicotine or other substances made or derived from tobacco may still be components or parts and, therefore, subject to the FDA’s tobacco control authorities.

Cassels-Smith says that Zanoprima has filed multiple global patents for its technologies and has also begun the process of filing drug master files with the FDA for SyNic nicotine, SyNic bitartrate and SyNic polacrilex resin. “Coupled with e-LiquiTech’s exclusive distribution, competitive pricing and carrying the e-LiquiTech guarantee, these products will be available only to responsible partners operating within the regulatory guidelines of the global tobacco industry,” said Cassels- Smith. “The synthetic nicotine is cleaner than naturally derived nicotine because it has no TSNAs. These nitrosamines have the potential to turn into carcinogens. SyNic will not have any nitrosamines and is 100 percent carcinogenic-free by design.”

E-LiquiTech’s synthetic nicotine resembles its naturally derived cousin. Like a naturally derived liquid nicotine, e-LiquiTech’s new synthetic nicotine is more than 99 percent pure (S)-nicotine. This purity of (S)-nicotine has a better effect on the body, and SyNic carries fewer impurities than naturally derived nicotine that comes from leaf tobacco.

“Nicotine exists in nature in two forms, (R) isomer and (S) isomer. One is basically a mirror image of the other, but the nicotine desired by vapers and smokers alike is the (S)-nicotine alone. Naturally grown tobacco contains over 99 percent (S)-nicotine, and the rest is very little (R),” says Cassels-Smith. “The body considers (R)-nicotine a filler with substantially less physiological effect. It’s considered a waste product, and [the body] does not absorb it. SyNic is slightly superior to the (S)-nicotine content found in a naturally derived nicotine because of its higher levels of (S)-nicotine with qualified and quantified impurities.”

Traditionally, a problem for the producers of synthetic nicotine has been that the entire production process is both complicated and expensive. As a chiral molecule, nicotine is far easier to produce as a synthetic nicotine with equal amounts of both (R) isomers and (S) isomers compared to a nearly pure (S)-nicotine. “(R)-[nicotine]/(S)-nicotine requires additional refining processes, which [are] time consuming and expensive to convert it to a true synthetic (S)-nicotine,” explains Cassels-Smith. “Also, because (R)-nicotine has substantially [fewer] physiological properties, it takes twice as much 50/50 synthetic nicotine in an e-liquid to achieve parity with SyNic. Because SyNic has greater than 99.7 percent (S), it only needs half the amount of SyNic to create the same effect for users as current synthetic nicotine offerings on the market.”

Naturally derived nicotine and synthetic nicotine are identical on a molecular level. The differences are the individual or potential impurities. Nicotine derived from tobacco can contain potentially harmful impurities if it is not purified sufficiently. That can be very difficult and costly because the impurities appear structurally very similar to the nicotine molecule itself. But synthetic nicotine is virtually free of any impurities from the beginning and none are carcinogenic.

SyNic, by design, carries no heavy metals and contains no residual pesticides. Additionally, unlike tobacco-derived nicotine that uses harsh acids and chemical solvents in its process, SyNic, is produced using a “green chemistry” method. “Its manufacturing is environmentally friendly, and any solvent used is recovered completely before being recycled for future use,” explains Cassels-Smith. “The SyNic process makes the tobacco-derived nicotine process appear dirty by comparison.”

SyNic will help manufacturers meet the FDA’s goals by consistently creating high-quality nicotine to deliver to the consumer without the possibility of potential carcinogens, according to Cassels-Smith. “We will allow vaping products to have the cleanest delivery and the best delivery,” he says. “That isn’t going to happen with the old technology. SyNic is a new frontier and a perfect tool for this industry to reinvent itself. It is constantly developing and reinventing itself. This product can help make all tobacco products better.”

Because of its unique patented process, Cassels-Smith says SyNic can achieve price parity with tobacco-derived nicotine. He adds, however, that this synthetic product will always be marketed at a higher cost than naturally derived nicotine to ensure there will always remain a naturally derived pedigreed nicotine market where the tobacco farmer can sell his crops.

“We have a lot of respect for the natural product and foresee our synthetic nicotine being a compliment to those that wish to remain all natural. There is enough room in the market for everybody. SyNic, with its known qualities, will have a place at the table alongside pedigreed natural tobacco-derived nicotine. But there are issues with nicotine sourced from scrap and dust as traceability is impossible and controlling pesticide and heavy metal contamination is problematic,” Cassels-Smith explains. “I foresee a future requiring the tracing of [natural] nicotine’s origin from the seed and soil through the extraction process and also quantifying impurities, all in cGMP facilities.”

SyNic’s potential is unlimited in the number of products in which it could be used. Cassels-Smith says that he cannot think of a single nicotine product that could not benefit from SyNic. In a heat-not-burn product, for example, during the rod-making process, SyNic could augment the prevalent nicotine source—or even be the sole source.

“Zanoprima has adapted their SyNic technology and patented an extremely unique and stable nicotine salt that does not use organic acids and retains pH stability,” he says. “SyNic also has the potential for being associated with superior purity and shelf life stability in all tobacco products of the future. SyNic will raise the bar, and we are just scratching the surface. It is a great tool that emerges at the perfect time for every tobacco product designer. The portfolio of potential products that can utilize SyNic is infinite.”