Preservatives liquid oral preparations

Ethanol preserves in concentrations above 15 % v/v. If sufficient ethanol is present in oral preparations, no other preservatives are needed. See Table 5.19 however for the restrictions for oral liquids for children. 

For the preservation of oral liquids and dermatological preparations at pH <5, sorbic acid or methyl parahydroxybenzoate is used, at pH 5-7 methyl parahydroxybenzoate, and at pH >7-8.5 methyl parahydroxybenzoate, even though its preservative effect is weak. It is therefore advised to reduce the pH or pay extra attention to the prevention of contamination. 

The hydroxybenzoic acid esters are among the most widely used preservatives in pharmacy preparation. They are used in oral liquids, enemas and cutaneous preparations. They are not very active against gram-negative bacteria. The combination with disodium edetate is not commonly used although it may overcome this drawback. 

Ethanol has long been employed as a solvent in pharmaceuticals. Since it also acts as a preservative and flavoring agent, it is second only to water in its use in liquid preparations. It has also been suggested that it may enhance the oral absorption of some active ingredients [71],... 

Some compounded preparations are naturally preserved, as in the case of certain syrups and elixirs others require the addition of a preservative. Preservatives are commonly added to products to minimize microbial growth, as in the case of oral liquids, topicals, and multi-dose parenterals. A preservative is selected based upon its characteristics, including concentration, pH, taste, odor, and solubility. 

Liquid dosage forms. The liquid products are prepared by dissolving the ingredients in the appropriate solvent systems. Dyes, flavors, sweeteners, and antimicrobial preservatives are added to mask unpleasant taste or appearance, and to prevent mold and bacterial growth. The final products are stored in large tanks before final packaging. If the liquid is used for injection or ophthalmic use, the liquid must be sterilized. Solutions for external or oral use do not require sterilization but generally contain antimicrobial preservatives [16, 17]. 

The other three classes of preservatives have been widely used in ophthalmic, nasal, and parenteral products, but not frequently in oral liquid preparations. The neutral preservatives are volatile alcohols their volatility introduces problems of odor and loss of preservative on aging in multidose preparations. The mercurials and quaternary ammonium compounds are excellent preservatives but are subject to incompatibilities.Mercurials are readily reduced to free mercury, and the quaternary compounds are inactivated by anionic substances. 

Van-Doorne H, Leijen JB. Preservation of some oral liquid preparations replacement of chloroform by other preservatives. Fharm World Sci 1994 16(Feb 18) 18-21. 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

Compared to tablets and capsules, oral liquids have some disadvantages as well. Their extemporaneous formulation and preparation is not so easy. They may have an tmpleasant taste, the use of solvents and preservatives is restricted due to their toxicity (especially for children), and the safe use of suspensions requires proper shaking. 

If the oral liquid has been prepared from an oral sohd using potable water, it has to be added immediately after preparation, thereby causing no larger microbiological load than that of potable water. Oral liquids made fi om raw materials are preserved in most cases and thus have a low bioburden. 

The pH is important for the preservative effect of sorbic acid and parahydroxybenzoic acid esters. These substances are most effective at pH <5. Since sorbic acid decomposes faster at low pH, pH 5 is used as a compromise (see Sect. 23.8.6). At a pH above 5.5-6.0, sorbic acid is not effective at all. At pH 7-8.5, the effectiveness of the parahydroxybenzoic acid esters is strongly reduced, in part due to their chemical instability. This implies that for dermatological preparations with a pH > 7, or in case of hypersensitivity for parahydroxybenzoic acid esters already > 5, the pharmacist has to resort to propylene glycol or probably phenoxyethanol. In case of an oral liquid with such a pH,... 

Syrups are a very commonly used form of sugars. They contain approximately 45-65 % of sugar, water and a preservative. Sometimes a flavouring is added. The preservative is most often methyl parahydroxybenzoate 0.1-0.15 %. Syrups can be very useful for improving the taste of oral liquid preparations and sometimes they can be used to stabilise a solubilisate of oil and polysorbate, e.g. in a vitamin A micellar solution (Table 23.12). 

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