Published May 16, 2025 | Version v1
Journal article Open

DESIGN AND EVALUATION OF BENZYL- AND DODECYL-BASED QUATERNARY AMMONIUM COMPOUNDS AS POTENTIAL COSMETIC PRESERVATIVES

Authors/Creators

  • 1. P. R. Patil Institute of Pharmacy, Talegaon (S.P.), Maharashtra, India.

Description

This study presents the synthesis, characterization, and biological evaluation
of two novel quaternary ammonium compounds (QACs):
Benzyltrimethylammonium chloride (QAC-1) and
Dodecyltrimethylammonium bromide (QAC-2), with a focus on their
potential as cosmetic preservatives. QAC-1 and QAC-2 were synthesized via
alkylation reactions and characterized by FTIR spectroscopy, which
confirmed the presence of key functional groups such as C–H stretching and
N⁺–CH₃ vibrations. Theoretical and practical yields were calculated, with
QAC-1 showing a significantly higher yield (78.08%) compared to QAC-2
(39.99%). Antibacterial activity was assessed using the cup plate method,
where QAC-1 exhibited a larger zone of inhibition (4.0 cm) than the
standard cetrimide (3.5 cm), while QAC-2 showed moderate activity (3.2
cm). Compatibility studies with common cosmetic excipients revealed good
stability of both QACs with hydrophilic substances like glycerin and
propylene glycol, whereas lipophilic excipients such as stearic acid and cetyl
alcohol led to phase separation or precipitation. These findings highlight
QAC-1 as a promising candidate for application as a novel cosmetic
preservative, particularly in water-based formulations. Further toxicological
and formulation studies are recommended to explore their full potential.

Files

10 WJAPS 140.pdf

Files (493.5 kB)

Name Size Download all
md5:187b5eacecc4826c89ca92e2e8c5983c
493.5 kB Preview Download

Additional details

References

  • Lundov, M. D., Moesby, L., Zachariae, C., & Johansen, J. D. (2009). Contamination versus preservation of cosmetics: A review on legislation, usage, infections, and contact allergy. Contact Dermatitis, 60(2): 70–78.
  • Geis, P. A. (2006). Cosmetic Microbiology: A Practical Approach. CRC Press.
  • Kabara, J. J., & Orth, D. S. (1997). Preservative-Free and Self-Preserving Cosmetics and Drugs: Principles and Practices. CRC Press.
  • Elder, R. L. (1984). Final report on the safety assessment of benzalkonium chloride. Journal of the American College of Toxicology, 3(5): 13–48.
  • Soni, M. G., Carabin, I. G., & Burdock, G. A. (2005). Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food and Chemical Toxicology, 43(7): 985–1015.
  • de Groot, A. C., & White, I. R. (2001). Cosmetics and skin allergies. Contact Dermatitis, 45(4): 215–216.
  • McDonnell, G., & Russell, A. D. (1999). Antiseptics and disinfectants: Activity, action, and resistance. Clinical Microbiology Reviews, 12(1): 147–179.
  • Gilbert, P., & Moore, L. E. (2005). Cationic antiseptics: Uses and action. Journal of Applied Microbiology, 99(4): 703–715.
  • Satari, M., Fazeli, A., Jamalifar, H., & Samadi, N. (2012). Synthesis and antibacterial activity of some novel quaternary ammonium salts. Molecules, 17(10): 12108–12120.
  • Orth, D. S., Applegate, B. M., & Wu, X. (2014). Quaternary ammonium compounds: Assessment of potential skin and respiratory irritation. Regulatory Toxicology and Pharmacology, 70(3): 567–575.
  • Langsrud, S., Sundheim, G., & Holck, A. L. (2016). Mechanisms of resistance to quaternary ammonium compounds in Pseudomonas aeruginosa. International Journal of Food Microbiology, 216: 1–7.
  • Zheng, J., Wang, Y., Zhu, Y., & Chen, H. (2013). Synthesis and biodegradation of novel biodegradable quaternary ammonium salts. Journal of Surfactants and Detergents, 16(5): 681–687.
  • Smith, B. C. (2011). Fundamentals of Fourier Transform Infrared Spectroscopy. CRC Press.
  • Lygo, B.; Andrews, B.I. Asymmetric Phase-Transfer Catalysis Utilizing Chiral Quaternary Ammonium Salts: Asymmetric Alkylation of Glycine Imines. Acc. Chem. Res., 2004; 37: 518–525.
  • Jones, R.A. Quaternary Ammonium Salts: Their Use in Phase-Transfer Catalysis; Elsevier: Amsterdam, The Netherlands, 2000.
  • Saurino, V.R. Germicidal Use of Compositions Containing Certain Quaternary Ammonium Compounds. U.S. Patent 4,321,277, 23 March 1982.
  • Chen, C.Z.; Beck-Tan, N.C.; Dhurjati, P.; van Dyk, T.K.; LaRossa, R.A.; Cooper, S.L. Quaternary Ammonium Functionalized Poly(Propylene Imine) Dendrimers as E ective Antimicrobials: Structure-Activity Studies. Biomacromolecules, 2000; 1: 473–480.
  • Okeke, Ugochukwu C., Chad R. Snyder, and Stanislav A. Frukhtbeyn. "Synthesis, purification and characterization of polymerizable multifunctional quaternary ammonium compounds." Molecules, 2019; 24.8: 1464.
  • Sommer, Harold Z., and Larry L. Jackson. "Alkylation of amines. New method for the synthesis of quaternary ammonium compounds from primary and secondary amines." The Journal of Organic Chemistry, 1970; 35.5: 1558-1562.
  • Sommer, Harold Z., Hayden I. Lipp, and Larry L. Jackson. "Alkylation of amines. General exhaustive alkylation method for the synthesis of quaternary ammonium compounds." The Journal of Organic Chemistry, 1971; 36.6: 824-828.
  • Thorsteinsson, Thorsteinn, et al. "Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds." Journal of Medicinal Chemistry, 2003; 46.19: 4173-4181.