Cetylpyridinium chloride (CPC) vs Chlorhexidine: What's the Difference?

There are a large number of mouth rinse products available to the general public. Many have not been thoroughly evaluated and relatively few comparisons of products have been made. 

In this article, we would like to cover 2 popular mouths rinse products i.e. cetylpyridinium chloride (CPC) and chlorhexidine.

What is Cetylpyridinium Chloride (CPC)?

Cetylpyridinium chloride (CPC) is obtained by quaternization of pyridine with cetyl chloride.

CPC functions by penetrating the cell membrane. This causes cell components to leak, which eventually leads to cell death. It is a well-known antimicrobial agent used in mouthwash to promote gingival health. It has also been used as an antiseptic when treating infections in the mouth and throat.

Cetylpyridinium Chloride Dangers

Cetylpyridinium chloride in mouthwash has been misattributed as a cause of oral cancer in the past, but research has not shown it to link to any form of cancer – no more than any other compound used in mouthwash. The risks of CPC are minor; it is only toxic in large doses (1 gram or more of pure CPC, ingested) and as an antimicrobial spray on food, it is far more helpful than harmful. 

Frequent and heavy use of a CPC-based mouthwash or toothpaste can bring side effects, however. Frequent use of CPC-based oral hygiene products can cause minor brown staining on teeth, a slight burning sensation in the gums and the products have been found to promote the formation of calculus (also known as tartar) on some users' teeth. None of these side effects are particularly harmful, but they should be considered.  

 

What is Chlorhexidine Gluconate?

Chlorhexidine mouthwash has the most ideal properties — antiviral action plus substantivity- to act as an antiviral mouthwash and throat gargle against all enveloped viruses, esp. SARS-CoV-2.

We should use the old and newer lines of evidence and educate the people and help them make use of chlorhexidine mouthwash to eliminate the virus from the oropharyngeal region and reduce the transmission of the virus.

Chlorhexidine gluconate, as a mouthwash and throat gargle, has the ability to work as an effective agent in pre-exposure as well as post-exposure prophylaxis.

Chlorhexidine gluconate will be of great use in clinics to minimize the exposure of healthcare workers to the SARS-CoV-2 virus and safeguard their health.

Along with safe distancing, proper use of masks, hand sanitization, and eyewear, chlorhexidine can reduce virus transmission effectively, safeguard the doctors and clinics, offices, and households from indoor transmission.

It can also help hospitalized patients to reduce their oropharyngeal viral load effectively.

This way, chlorhexidine can help reduce infection as well as infectivity. Thus, it will help us minimize community transmission and control the pandemic crisis. 

Cetylpyridinum Chloride vs Chlorhexidine for Dental Plaque

This study (Periodontol 1996) compared 4 mouthrinse products containing cetylpyridinium chloride (CPC), chlorhexidine, C31G, or triclosan with saline rinse included as a placebo control. 

Method: Twenty dentate volunteers took part in this 4-day plaque regrowth study which had a single blind, randomized cross-over design balanced for residual effects. On day 1 of each study period, volunteers were rendered plaque free by a professional prophylaxis, suspended normal oral hygiene measures, and rinsed twice daily for 1 minute with 15 mL of the allocated rinse. On day 5, subjects were scored for disclosed plaque by plaque index and plaque area. 

Results: By both measures the order of decreasing product efficacy was chlorhexidine, CPC and triclosan, C31G, and saline. All the differences in favor of the chlorhexidine product were highly significant as were those in favor of the other rinses compared to saline. 

Editor's Note: In this study, chlorhexidine was more effective than CPC.

Conclusion: It is concluded that the findings of this study reflect the actual chemical benefits of the products divorced from the indeterminate variable of toothbrushing.

Cetylpyridinum Chloride vs Chlorhexidine for COVID-19

A scientific review, published in the Journal of Formosan Medical Association (October 2021) concluded that mouthwash containing CPC shows potential for reducing the viral load of COVID-19 virus in the throat.

Evidence as a mouthwash against COVID-19 infection: CPC

Three in vitro studies supported the virucidal effect of CPC-containing mouthwash against SARS-CoV-2 infection. Meyers et al. demonstrated that 0.07% CPC inactivated ≥99.9% of SARS-CoV-2 within 30–120 s of incubation. Komine et al. also demonstrated that mouthwashes containing 0.04–0.075% CPC inactivated >99.99% of SARS-CoV-2 in 20–30 s. Munoz-Basagoiti et al. investigated the antiviral effect of CPC on the D614G and Alpha SARS-CoV-2 variants. They demonstrated that a 2-min incubation with 10 mM (0.35%) CPC suppressed viral fusion by disrupting the viral envelope, thus inhibiting virus entry into target cells. They also demonstrated that a 30-s incubation with 2 mM (0.07%) CPC in the presence of sterilized saliva still inactivated ≥99.9% SARS-CoV-2, even at a dilution ratio of 1:10.

A RCT conducted in Singapore revealed that, compared with COVID-19 patients using water rinses, 4 patients prescribed 30 s of exposure to 0.075% CPC mouthwash exhibited a significantly reduced load of SARS-CoV-2 in 5 min and the effect persisted for 6 h. Eduardo et al. also prescribed 30 s of exposure to 0.075% CPC mouthwash to 7 COVID-19 patients and demonstrated that, compared with the baseline, viral load was significantly reduced for up to 60 min.

Evidence as a mouthwash against SARS-CoV-2 infection: Chlorhexidine

The in vitro evidence of CHX against SARS-CoV-2 is controversial. Jain et al. demonstrated that 30–60 s of incubation with 0.12–0.2% CHX inactivated ≥99.9% of SARS-CoV-2. However, Meister et al. reported that a 30-s incubation of 0.2% CHX modestly reduced the load of SARS-CoV-2 (70–90%; <1 log10 reduction), and Davies et al. reported similar results with a 1-min incubation period. Komine et al. reported that 30-s incubation with 0.12% CHX achieved only 42.5% virus reduction after 10 min. By further extending the incubation period to 10 min, Steinhauer et al. demonstrated that 0.1–0.2% CHX could only inactivate <90% (<1 log10 reduction) of SARS-CoV-2.

Although a small RCT conducted in Singapore did not reveal significant differences in the reduction of SARS-CoV-2 between patients prescribed 30 s of 0.2% CHX exposure and those prescribed water rinses, a larger RCT conducted in the United States demonstrated that by following a 4-day course of 0.12% CHX oropharyngeal rinse (30-s exposure, twice daily), SARS-CoV-2 was eliminated from the oropharynx in 62.1% of COVID-19 patients. Another small RCT conducted in Brazil showed that a 30-s 0.12% CHX rinse significantly reduced the load of SARS-CoV-2 in saliva for up to 60 min.

Editor's note: Based on the comparative RCT conducted in Singapore, CPC exhibited a significant reduced viral load whereas differences in viral load was not significant for Chlorhexidine.

Chlorhexidine vs Povidone Iodine vs Colgate Peroxyl vs Listerine? 

 Promising research has been conducted by the Rutgers School of Dental Medicine which tested various commercially available mouthwashes against the COVID-19 virus. For this study, they used Colgate Peroxyl (hydrogen peroxide), povidone-iodine, chlorhexidine gluconate, and Listerine (essential oils and alcohol). They tested these mouthwashes in vitro, under conditions simulating the oral cavity, and determined their antiviral properties independent of their cytotoxicity. They tested the mouthwashes for 20 seconds and 2 hours, using different dilutions.

Results: On testing the different mouthwashes on the viability of cells, all four of them at 100% dilution were highly cytotoxic. The mouthwash least toxic to the cells was Listerine and chlorhexidine gluconate was a close second. On further analysis, when epithelial cells were exposed to the mouthwashes for 2 hours, 6.3% (v/v) diluted Listerine and 1.5% (v/v) diluted chlorhexidine gluconate do not affect the viability of cells. A minimal dilution of 0.1% (v/v) of Colgate Peroxyl or povidone-iodine still showed cytotoxic properties.

On testing the antiviral properties of the mouthwashes, 3% (v/v) dilution of Listerine and 1.5% (v/v) dilution of chlorhexidine gluconate minimized the SARS-CoV-2 infection by 40% and 70%, respectively. This is without any significant effect on the cell morphology. On the other hand, 0.05% (v/v) dilution of Colgate Peroxyl and 0.1% (v/v) dilution of povidone-iodine also showed antiviral properties but with significant cell damage. This result is evident that the antiviral effect of Colgate Peroxyl and povidone-iodine is a result of its cytotoxic properties.

On testing the direct effect of mouthwashes on the virus, Colgate Peroxyl and povidone-iodine inactivate COVID-19 more effectively than chlorhexidine gluconate and Listerine. However, their inhibitory effect on the virus is interlinked with cytotoxicity.

This research was important in distinguishing the difference between the antiviral properties of the mouthwash and its cytotoxic properties.

Cetylpyridinium chloride Mouthwash (Amazon)