## 1 Introduction  
Oral biofilms are the main causative factor for caries, periodontal diseases, periimplant diseases and oral halitosis. Hence, an adequate regular control of oral biofilms is critical not only to maintain oral health but also to prevent recurrent disease [1, 2]. Therefore, since epidemiological and intervention studies have shown an association between periodontitis and the onset and progression of different systemic diseases, oral biofilm control is also important for maintaining overall health [3]. An efficient regular mechanical oral biofilm control is difficult to achieve and is limited by both subject-related factors such as poor motivation or education and lack of adequate compliance; and/or skills and tooth-related factors, such as the limited use of interdental cleaning devices and the presence of hard-to-reach areas. As a consequence, there is clear evidence [4, 5] that for some patients, mechanical biofilm control is not sufficient for preventing or controlling oral diseases. In these patients, the adjuvant use of chemical agents with antimicrobial effects, as mouthwashes or toothpastes, has shown to be useful in dental biofilm control and maintenance of oral/periodontal health [6]. Furthermore, a recent published systematic review showed that antiseptic therapies used adjunctively to mechanical plaque control were equally effective in reducing gingivitis and plaque in patients with gingivitis on intact periodontium or in previously treated periodontitis patients with gingival inflammation [7]. Toothpaste, by combining the antimicrobial effect provided by its active ingredients, with the mechanical effect of toothbrushing, is the preferred method for controlling oral biofilms by both dentists and patients [6], and consequently, is the most widespread population-based oral hygiene method. Although chlorhexidine (CHX) is currently considered as the most effective and long-lasting antiplaque agent available [6], its widespread use is limited due to its side effects with prolonged use, including tooth and tongue pigmentation, taste alteration, mucous membrane irritation and hypersensitivity reactions [8]. Moreover, due to its high cationic nature, CHX-based toothpastes are difficult to formulate since other anionic substances, such as surfactants, may reduce its bioavailability and, consequently, its efficacy [6]. As an alternative, the use of cetylpyridinium chloride (CPC)-based toothpastes has been suggested for oral biofilm control [6]. The antimicrobial activity of CPC has been studied for more than 70 years with proven antimicrobial effect against Gram-positive bacteria, fungi and yeasts [9]. CPC-containing products are considered as safe and effective for the treatment of plaque-induced gingivitis by the Food and Drug Administration (FDA) [10]. Its efficacy, however, may depend on the specific formulation, due to its as stringent characteristics and the possible interactions with excipients or other components. Therefore, it is not uncommon to find two CPC products formulated with the same concentration, but with significantly different substantivity, bioavailability and ability to penetrate within the biofilm, which may significantly impact its efficacy [11]. To overcome some of these limitations, other substances with biological activity synergistic with CPC have been added to oral hygiene products [12]. In fact, the FDA has recognized the effectivity of natural products such as plant extracts and the essential oils of eucalyptus, menthol, methyl salicate and thymol (cymenol) in mouth rinses and toothpastes due to their antibacterial and antib Biofilm properties. [PERSON] et al. [13] confirmed that the use of a 0.1% cynenol-containing toothpaste over a 12-week period provides a statistically significant benefit maintaining gingival health as compared to a sodium fluoride control toothpaste. Moreover, a recent study concluded that CPC and cynenol formulated in mouth rinses may act synergistically, extending the substantivity of their action [14].