Small Volume Parenterals 519 ‘These are commonly used in ophthalmic preparations. Usually alcohols and esters are used in parenteral preparations. While selecting a preservative the stability of the product and effectiveness of the preservative along with other additives in the formulation should be considered, Preservative may be inactivated by surfactants and rubber closures may bind with preservative’, The macromolecules bind the preservatives and reduce the antimicrobial activity’* considerably. Total paraben Effective cone. (14) of preservative Free paraben Investigation on interaction between polysorbate 21 80, a nonionic surfactant, and methylparaben reveals that polysorbate 80 can reduce the concentration of free antimicrobial agent (Fig. 14.5). The plots are linear and can be expressed as; R Total concentration of preservative Free preservative concentration Conc. of polysorbate 80 (w/v) Fig. 14.5 Effect of polysorbate 80 (on the antimicrobial activity of 1+kM methylparaben on the growth of aerabacter aerogenes where Ris kis the slope and Mis the concentration of surfactant. Significant loss of preservative from a solution due to rubber stoppers and rubber extractives has ‘Table 14.5 Minimum inhibitory concentration (MIC) and commonly used cancentration of some preservatives been found. The preservative Commontyused efficiency can be tested by measuring | Preservative | MICU) | concentration (4) the bacteriostatic or bactericidal | Genzalkonium | 0.005 -0.03 001 activity of the preservative against | chloride 10-100 10 selected microorganism(s). The USP | Benzylakahol | 02-08 os hhas a standard method for this test’ | chiorobutanot_ | 01-03 02 Such test should be conducted on a | Chlorecresol | 01-06 03 formulation during its shelf life and | Cresol 0.05 -0.25 02 near to its expiration date to assure | Parabens 01-08 05 the presence of required amount of | Phenol 0.001 -0.05, 0.002 preservative. Table 14.5 presents the | Phenvimercurc | 0.001 0.03, 002 minimum inhibitory concentration | Pate (Mic) and commonly used concen. Themersal tration of some preservatives. Ul O <