Polysorbate 80 incompatibility

Antimicrobial activity benzyl alcohol is bacteriostatic and is used as an antimicrobial preservative against Gram-positive bacteria, molds, fungi, and yeasts, although it possesses only modest bactericidal properties. Optimum activity occurs at pH below 5 little activity is shown above pH 8. Antimicrobial activity is reduced in the presence of nonionic surfactants, such as polysorbate 80. However, the reduction in activity is less than is the case with either hydroxybenzo-ate esters or quaternary ammonium compounds. The activity of benzyl alcohol may also be reduced by incompatibilities with some packaging materials, particularly polyethylene see Section 12. 

Sulfhydryl compounds cause significant reductions in the activity of bronopol, and cysteine hydrochloride may be used as the deactivating agent in preservative efficacy tests lecithin/ polysorbate combinations are unsuitable for this purpose. Bronopol is incompatible with sodium thiosulfate, with sodium metabisulfite, and with amine oxide or protein hydrolysate surfactants. Owing to an incompatibility with aluminum, the use of aluminum in the packaging of products that contain bronopol should be avoided. 

Owing to problems associated with sorption, chlorobutanol is incompatible with plastic vials, rubber stoppers, bento-nite, magnesium trisilicate, polyethylene, and polyhydroxy-ethylmethacrylate, which has been used in soft contact lenses. ° To a lesser extent, carboxymethylcellulose and polysorbate 80 reduce antimicrobial activity by sorption or complex formation. 

Incompatible with oxidizing agents and protein, e.g., serum. Phenylethyl alcohol is partially inactivated by polysorbates, although this is not as great as the reduction in antimicrobial activity that occurs with parabens and polysorbates. ... 

Polysorbate (Tween 20 and 80) and Cremophor RH40 (macrogol glycerol hydroxyl stearate) or Cremophor EL (polyoxylated 35 castor oil) can cause serious hypersensitivity reactions when administered parenterally [15]. They may cause incompatibilities by leaching plasticisers (such as phthalates) from polyvinyl chloride infusion devices. 

Gillissen [104] finds that the antibacterial action of tyrothricin is influenced by the presence of solubilizers. Cationic surfactants have a synergistic effect (as mentioned above) on its activity against Gram-positive and Gram-negative bacteria, whereas polysorbate 80 inhibits its activity. It is thus important that these effects are borne in mind, and a compromise must be found between the stability and incompatibility characteristics of the solution and the activity of the product. The complexity of the situation is revealed by the fact that the activity of bacitracin is enhanced by the presence of cationic and non-ionic surfactants [106] but decreased by anionic agents. The effect of non-ionic surfactants on the bactericidal activity of tyrothricin has been measured [107]. Some results are shown in Table 6.11. 

The solubility of dihydrostreptomycin sulphate, which is water soluble, is decreased in concentrated solutions of sorbitan monolaurate (E = 12) [129]. Streptomycin sulphate is also very soluble in water and is incompatible with sodium lauryl sulphate. Combination of streptomycin with polysorbate 20 produces a strong bacteriostatic effect against antibiotic resistant bacteria. Intrapleural injection of 0.5 g dihydrostreptomycin with one drop of polysorbate 20 in 4 ml has been reported to result in a sterile pleural sample 1 week after injection [130]. 

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