Excipients antimicrobial effect

The multidose formulation will be tested to determine its efficacy according to the Antimicrobial Effectiveness Test required by the USP.39 If the results support the USP requirements, international requirements must then be met. International markets require different preservatives, different concentrations, and different excipients of the formulation. In addition, the period required for the inhibition and/or killing of the challenge microorganisms may be different. International regulatory requirements for compliance should be well researched and understood by the scientific and the management staff. 

Some active substances or excipients have an antimicrobial effect not only through reducing the water activity, but also through a specific antimicrobial mechanism. The best-known example is propylene glycol, but also ethanol, local anaesthetics, chlorpromazine hydrochloride, promethazine hydrochloride and essential oils exhibit a specific antimicrobial effect. In addition, the combination of weak antimicrobial effects of disodium edetate, borax, and boric acid appeared to justify prolongation of the shelf life of non-preserved eye drops over the standard limit of 24 h [48]. 

This aromatic alcohol has been an effective preservative and still is used in several ophthalmic products. Over the years it has proved to be a relatively safe preservative for ophthalmic products [138] and has produced minimal effects in various tests [99,136,139]. In addition to its relatively slower rate of activity, it imposes a number of limitations on the formulation and packaging. It possesses adequate stability when stored at room temperature in an acidic solution, usually about pH 5 or below. If autoclaved for 20-30 minutes at a pH of 5, it will decompose about 30%. The hydrolytic decomposition of chlorobutanol produces hydrochloric acid (HC1), resulting in a decreasing pH as a function of time. As a result, the hydrolysis rate also decreases. Chlorobutanol is generally used at a concentration of 0.5%. Its maximum water solubility is only about 0.7% at room temperature, which may be lowered by active or excipients, and is slow to dissolve. Heat can be used to increase dissolution rate but will also cause some decomposition and loss from sublimation. Concentrations as low as 0.125% have shown antimicrobial activity under the proper conditions. 

Chlorocresol is used as an antimicrobial preservative in cosmetics and pharmaceutical formulations. It is generally used in concentrations up to 0.2% in a variety of preparations except those intended for oral administration or that contact mucous membrane. Chlorocresol is effective against bacteria, spores, molds, and yeasts it is most active in acidic media. Preservative efficacy may be reduced in the presence of some other excipients, particularly nonionic surfactants, see Sections 10 and 12. 

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