Evaluation of new formulations for neutralizing antimicrobial preservatives in pharmaceutical preparations

BACKGROUND: Neutralization of preservative systems is essential to obtain reliable results when testing samples containing preservatives such as nutritional, cosmetic and pharmaceutical products. Therefore, the aim of this study was to prepare and investigate the neutralization ability of in-house neutralizing systems made of available cost-effective materials in the inactivation of preserved pharmaceutical suspensions. Ibuprofen and Cefpodoxime proxetil preserved suspensions were chosen as the quenching model since subsequent microbiological studies will be conducted on their local pharmaceutical formulations available in the Syrian market. METHODS: We reported toxicity and efficacy ratios of ten neutralizing systems (No.1 to No.10) containing polysorbate 80, cetomacrogol 1000 and polyoxyl 40 hydrogenated castor oil with various concentrations dedicated to the inactivation of Ibuprofen and Cefpodoxime proxetil preserved suspensions, methyl paraben/propyl paraben mixture and sodium benzoate controls against low inoculum ranging between 1 × 10(2)–1.2 × 10(3) CFU of five challenged bacteria and fungi; Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and another environmental isolate of Aspergillus niger. Neutralizing systems validation was conducted according to USP chapter 1227 criteria to assess the acceptance of recovery comparisons for both “Neutralizing systems toxicity test” and “Neutralizing systems efficacy test” which enabled determining the appropriate neutralizing formula for both neutralization of preservative system of a specified product and being non-toxic towards the challenged microorganism additions. RESULTS: Most neutralizing formulas used in the study were non-toxic for all tested microorganisms. According to “Neutralizing systems efficacy test”, No. 3 (polysorbate 80 (3%)) and No. 10 (polysorbate 80 (1%), cetomacrogol 1000 (1%) and polyoxyl 40 hydrogenated castor oil (1%)) effectively recovered at least three microorganisms when used in the neutralization of samples. Most limitations were observed when neutralizing ibuprofen suspension. However, we found neutralizing system No. 10 against Pseudomonas aeruginosa, No. 3 and No. 5 against Escherichia coli and No. 8 and No. 10 against Candida albicans were effective in the neutralization of ibuprofen suspension. All neutralizing systems effectively inactivated the preservative system of cefpodoxime proxetil suspension using all microorganisms while several neutralizing systems failed in quenching cefpodoxime proxetil suspension against Staphylococcus aureus. CONCLUSION: Due to the variation in the neutralization efficacy relative to the product sample and challenged microorganism, neutralization validation procedure must be undertaken before microbiological testing of pharmaceuticals which makes the development and validation of neutralizing systems an essential procedure.