AAPS PharmSciTech

, 20:248 | Cite as

Dentifrice Based on Fluoride–Hydrotalcite Compounds: Characterization and Release Capacity Evaluation by Novel In Vitro Methods

  • Cinzia Pagano
  • Luana PerioliEmail author
  • Fabio Marmottini
  • Daniele Ramella
  • Maria Cristina Tiralti
  • Maurizio Ricci
Research Article


Anti-caries activity of fluoride ions is due to the protection against demineralization and the enhancement of remineralization of tooth enamel. Dentifrices available on the market contain sodium fluoride, sodium monofluorophosphate, stannous fluoride, and amine fluoride as source of these ions. A new compound working both as fluoride ion source and as abrasive was projected. Hybrids based on F ions intercalated between the lamellae of hydrotalcite-like compounds (HTlc-F), namely MgAl-HTlc-F and ZnAl-HTlc-F, were prepared and characterized. Then, three different percentages (2, 3, and 4%) of both HTlc-F compounds were assayed. After the rheological characterization, the dentifrices containing 3 and 4% of MgAl-HTlc-F and ZnAl-HTlc-F, respectively, resulted to be the most suitable ones. Two novel in vitro methods, “rotary toothbrush method” and “manual brushing method,” were developed and used in order to study the F ions release from the prepared dentifrices. The obtained results showed that the dentifrice containing ZnAl-HTlc-F (4%) was the most effective in releasing fluoride ions. The “rotary toothbrush method” resulted to be the most suitable as the simulation of the brushing movements is standardizable and reproducible.


hydrotalcite HTlc-F abrasive dentifrice rheology in vitro release method 



The authors are very grateful to Mr. Marco Marani for technical assistance.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2019_1459_Fig12_ESM.png (561 kb)

Figure 1SI. Thermogravimetric curves obtained from A) MgAl-HTlc-F and B) ZnAl-HTlc-F (PNG 561 kb)

12249_2019_1459_MOESM1_ESM.tif (19.3 mb)
High resolution image (TIF 19764 kb)
12249_2019_1459_Fig13_ESM.png (88 kb)

Figure 2SI. XRPD patterns of dentifrices F (containing ZnAl-HTlc-F 4%, red line) and H (containing MgAl-HTlc-F 3% blue line) (PNG 87 kb)

12249_2019_1459_MOESM2_ESM.tif (78 kb)
High resolution image (TIF 77 kb)


  1. 1.
    Horst JA, Tanzer JM, Milgrom PM. Fluorides and other preventive strategies for tooth decay. Dent Clin N Am. 2018;62:207–34.CrossRefGoogle Scholar
  2. 2.
    Walsh T, Worthington HV, Glenny AM, Appelbe P. Marinho VCC, Shi X. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents (review). Cochrane Database Syst Rev, 2010; 1: Art. No.: CD007868. DOI:
  3. 3.
    Lippert F. Introduction to toothpaste—its purpose, history and ingredients. In: van Loveren CA, editor. Toothpastes. Monogr Oral Sci. Basel. Amsterdam: Karger; 2013. p. 1–14.Google Scholar
  4. 4.
    Margolis HC, Moreno EC. Physicochemical perspectives on the cariostatic mechanisms of systemic and topical fluorides. J Dent Res. 1990;69(Spec Iss):606–13.CrossRefGoogle Scholar
  5. 5.
    Trifirò F, Vaccari A. In: M. Alberti, T. Bein, (Eds). Solid state supramolecular chemistry: two- and three-dimensional inorganic networks comprehensive supramolecular chemistry, Pergamon-Elsevier: Oxford, 7 (8) 1996, pp. 1–46.Google Scholar
  6. 6.
    Miyata S. Anion exchange properties of hydrotalcite-like compounds. Clay Clay Miner. 1983;31(4):305–11.CrossRefGoogle Scholar
  7. 7.
    Ulibarri MA, Pavlovic I, Barriga C, Hermosı́n MC, Cornejo J. Adsorption of anionic species on hydrotalcite-like compounds: effect of interlayer anion and crystallinity. Appl Clay Sci. 2001;18:17–27.CrossRefGoogle Scholar
  8. 8.
    Costantino U, Ambrogi V, Nocchetti M, Perioli L. Hydrotalcite-like compounds: versatile layered hosts of molecular anions with biological activity. Micropor Mesopor Mater. 2008;107:149–60.CrossRefGoogle Scholar
  9. 9.
    Perioli L, Nocchetti M, Giannelli P, Pagano C, Bastianini M. Hydrotalcite composites for an effective fluoride buccal administration: a new technological approach. Int J Pharm. 2013;454:259–68.CrossRefGoogle Scholar
  10. 10.
    Sanderson BA, Sowersby DS, Crosby S, Goss M, Lewis LK, Beall GW. Charge density and particle size effects on oligonucleotide and plasmid DNA binding to nanosized hydrotalcite. Biointerphases. 2013;8:8.CrossRefGoogle Scholar
  11. 11.
    Pagano C, Perioli L, Blasi F, Bastianini M, Chiesi C, Cossignani L. Optimization of wine phenol extraction by layered double hydroxides and technological evaluation of the bioactive rich compound. Int J Food Sci Technol IJFST. 2017;52(12):2582–8.CrossRefGoogle Scholar
  12. 12.
    Perioli L, Ambrogi V, Nocchetti M, Sisani M, Pagano C. Preformulation studies on host-guest composites for oral administration of BCS class IV drugs: HTlc and furosemide. Appl Clay Sci. 2011;53:696–703.CrossRefGoogle Scholar
  13. 13.
    Sani T, Adem M, Fetter G, Bosch P, Diaz I. Defluoridation performance comparison of nano-hydrotalcite/hydroxyapatite composite with calcined hydrotalcite and hydroxyapatite. Water Air Soil Pollution. 2016;227:90.CrossRefGoogle Scholar
  14. 14.
    Duceac LD, Dobre CE, Pavaleanu I, Calin G, Nichitus S, Damir D. Diseases prevention by water defluoridation using hydrotalcites as decontaminant materials. Rev Chim. 2017;68:168–71.Google Scholar
  15. 15.
    Cao Y, Guo Q, Zhuang Y, Yu Z, Guo W, Zhang C, et al. Removal of harmful constituents from geothermal water by selected anion clays. Proc Earth Planet Sci. 2017;17:161–4.CrossRefGoogle Scholar
  16. 16.
    Perioli L, Pagano C, Nocchetti M, Latterini L. Development of smart semisolid formulations to enhance retinoic acid topical application. J Pharm Sci. 2015;104:3904–12.CrossRefGoogle Scholar
  17. 17.
    Arrigo R, Ronchetti S, Montanaro L, Malucelli G. Effects of the nanofiller size and aspect ratio on the thermal and rheological behavior of PEG nanocomposites containing boehmites or hydrotalcites. J Therm Anal Calorim. 2018;134(3):1667–80.CrossRefGoogle Scholar
  18. 18.
    Yokogawa Y, Kakehashi K, Wakabayashi H, Oike K, Morita Y, Fujii K, et al. VSC adsorptive property of zinc or iron oxide in comparison with that of layered double hydroxide containing zinc of iron. Key Eng Mater. 2018;782:250–5.CrossRefGoogle Scholar
  19. 19.
    Yokogawa Y, Sano H, Namba S, Fujii K, Morita Y, Hotta M, et al. VSC adsorption capability of layered double hydroxide containing transition metal. J Biomim Biomat Biomed Eng. 2014;21:71–4.Google Scholar
  20. 20.
    Yokogawa Y, Namba S, Kinoshita J, Morita Y, Fujii K, Hotta M, et al. VSC sorption onto Mg-Fe-F layered double hydroxide and its fluoride release in aqueous solution. Key Eng Mater. 2016;720:37–40.CrossRefGoogle Scholar
  21. 21.
    Costantino U, Marmottini F, Nocchetti M, Vivani R. New synthetic routes to hydrotalcite-like compounds—characterisation and properties of the obtained materials. Eur J Inorg Chem. 1998;1998(10):1439–46.CrossRefGoogle Scholar
  22. 22.
    Bish DL. Anion exchange in takovite: applications to other hydroxide minerals. Bull Mineral. 1980;103:170–5.Google Scholar
  23. 23.
    Reichle WT. Synthesis of anionic clay minerals (mixed metal hydroxides, hydrotalcite). Solid State Ionics. 1986;22:135–41.CrossRefGoogle Scholar
  24. 24.
    Dionex, Determination of anions in acid rain, Application note 31, 1992.Google Scholar
  25. 25.
    Pauling L. The sizes of ions and the structure of ionic crystals. J Am Chem Soc. 1927;49:765–90.CrossRefGoogle Scholar
  26. 26.
    Tyle P. Effect of size, shape and hardness of particles in suspension on oral texture and palatability. Acta Psychol. 1993;84(1):111–8.CrossRefGoogle Scholar
  27. 27.
    Wülknitz P. Cleaning power and abrasivity of European toothpastes. Adv Dent Res. 1997;11(4):576–9.CrossRefGoogle Scholar
  28. 28.
    Lippert F, Arrageg MA, Eckert GJ, Hara AT. Interaction between toothpaste abrasivity and toothbrush filament stiffness on the development of erosive/abrasive lesions in vitro. Int Dental J. 2017;67:344–50.CrossRefGoogle Scholar
  29. 29.
    Camargo IM, Saiki M, Vasconcellos MB, Avila DM. Abrasiveness evaluation of silica and calcium carbonate used in the production of dentifrices. J Cosmet Sci. 2001;52(3):163–7.PubMedGoogle Scholar
  30. 30.
    Li Y, Hou WG, Shen SL. Rheological behaviour of aqueous suspension containing cationic starch and aluminum magnesium hydrotalcite-like compound in the presence of different electrolytes. Coll Surf A Physicochem Eng Aspects. 2009;350(1–3):109–13.CrossRefGoogle Scholar
  31. 31.
    Ritger P, Peppas NA. A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices. J Control Release. 1987;5:37–42.CrossRefGoogle Scholar
  32. 32.
    Bhaskar R, Murthy RSR, Miglani BD, Viswanathan K. Novel method to evaluate diffusion controlled release of drug from resinate. Int J Pharm. 1986;28:59–66.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Cinzia Pagano
    • 1
  • Luana Perioli
    • 1
    Email author
  • Fabio Marmottini
    • 2
  • Daniele Ramella
    • 3
  • Maria Cristina Tiralti
    • 1
  • Maurizio Ricci
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversità degli Studi di PerugiaPerugiaItaly
  2. 2.Department of Chemistry, Biology and BiotechnologyUniversità degli Studi di PerugiaPerugiaItaly
  3. 3.Department of Chemistry, College of Science and TechnologyTemple UniversityPhiladelphiaUSA

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