Evaluation of Neutralizing Efficacy and Possible Microbial Cell Toxicity of a Universal Neutralizer Proposed by the CTPA

Abstract

The purpose of this research was to study the neutralization efficacy of a universal neutralizer proposed by the CTPA on a range of antimicrobial agents and its potential toxicity for microorganisms that are used for antimicrobial preservation testing. Several types of antimicrobial agents including a mixture of methylisothiazolinone and its 5-chloro derivative, dimethylol dimethyl hydantoin, Quaternium-15 ® , Bronopol ® , benzalkonium chloride, phenoxyethanol, methyl and propyl paraben, chlorhexidine, imidazolidinyl urea, triclosan and thiomersal built-in pharmaceutical, cosmetic or health care products, as well as 6 types of these antimicrobials, i.e. a combination of methyl paraben (0.18% w/v) and propyl paraben (0.02%), imidazolidinyl urea (0.3%), chlorhexidine (0.01%), benzalkonium chloride (0.02%), Bronopol ® (0.1%) and thiomersal (0.02%) in their pure and soluble form were tested. Validation of microbial recovery was carried out according to the US Pharmacopeia 27 guidelines. The universal neutralizer could inactivate all the studied antimicrobial agents against different strains tested except Staphylococcus aureus. With regards to this microorganism, only seven preservative chemicals consisting of parabens, dimethylol dimethyl hydantoin, Quaternium-15 ® , Bronopol ® , benzalkonium chloride, Phenonip ® and imidazolidinyl urea were effectively inactivated. In addition, a pure solution of 0.02% thiomersal retained its antimicrobial properties against all studied microorganisms. The neutralizer solution showed no toxicity on any of the test organisms. In conclusion, CTPA proposed neutralizing solution is not an inclusive neutralizer. Moreover, each organism to be used in the test must be included in the validation study.