Para hydroxybenzoates, preservatives

TE Haag, DF Loncrini. Esters of para-hydroxybenzoic acid. In JJ Kabara, ed. Cosmetic and Drug Preservation. New York Marcel Dekker, 1984, pp 63-77. 

Liquid dosage forms which are disperse systems (colloidal, i.e., microspheres, nanoparticles, and micelles suspensions and emulsions) often contain preservatives which are methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid in various combinations. A typical example is the antacid suspensions which have high pH values which make the esters of the preservatives susceptible to hydrolysis. One way to circumvent this problem is to use several preservatives in combination with the hope that some quantities of the preservatives will remain to prevent the suspension from microbial attack. A report showing the assay of the four esters and the parent acid (one of the decomposition products) in drug products in which all the preservatives were used has been given [13]. 

A paired-ion, reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of sweeteners (dulcin, saccharin-Na, and acesulfame-K), preservatives (sodium dehydroacetate, SA, salicyclic acid, BA, succinic acid, methyl-para-hydroxybenzoic acid, ethyl-para-hydroxybenzoic acid, n-propyl-para-hydroxybenzoic acid, n-butyl-para-hydroxybenzoic acid, and isobutyl-para-hydroxybenzoic acid), and antioxidants (3-tertiary-butyl-4-hydroxyanisole and tertiary-butyl-hydroquinone). A mobile phase of acetonitrile-50 ml aqueous tr-hydroxyisobutyric acid solution (pH 4.5) (2.2 3.4 or 2.4 3.6, v/v) containing 2.5 mM hexadecyltrimethylammonium bromide and a Clg column with a flow rate of 1.0 ml/min and detection at 233 nm were used. This method was found to be very reproducible detection limits ranged from 0.15 to 3.00 p,g. The retention factor (k) of each additive could be affected by the concentrations of hexadecyltrimethylammonium bromide and a-hydroxyisobu-tyric acid and the pH and ratio of mobile phase. The presence of additives in dried roast beef and sugared fruit was determined. The method is suitable for routine analysis of additives in food samples (81). 

This group of chemicals, which are found naturally in many fruits, are used as preservatives, a function that they also perform within fruit. Benzoic acid itself may be used, or more commonly sodium benzoate (a salt) or ethyl or methyl para-hydroxybenzoate, also known as parabens. They have sometimes associated with adverse effects. Anaphylaxis-like reactions have been reported as well as urticaria. About 4 per cent of people who suffer from asthma may experience breathlessness and wheezing when exposed to benzoates. Parabens are often used as preservatives cosmetics. 

Parabens (methyl, ethyl, propyl, and butyl esters of para-hydroxybenzoic acid) are used as preservatives in concentrations of 0.1-0.3% in pharmaceutical formulations and in concentrations of 0.01-0.1% in cosmetics and foods. In such concentrations they are devoid of systemic toxic effects, but allergic reactions have been reported. 

Phenol acids are phenols in which there is also a carboxylic acid group attached to the benzene ring. They include salicylic acid (ortho-hydroxybenzoic acid) and para-hydroxy-benzoic acid (Figure 25.8). Acetylsalicylic acid (aspirin) and sodium salicylate are derivatives of salicylic acid. Like phenol, they have antipyretic and analgesic properties. The methyl, ethyl and propyl esters of para-hydroxybenzoic acid (parabens) are used as preservatives in pharmaceuticals, cosmetics and foodstuffs. 

Procaine, on the other hand, is an ester-type local anesthetic when it is injected into the organism, it is transformed into N,N-diethylaminoethanol and para-amino-benzoic acid (PABA) when the ester link that binds these two components of procaine is broken. PABA is a well-known allergen. Methyl para-hydroxybenzoate, whose structure is similar to that of PABA, is also called PAB or methylparaben. It is a preservative that binds, like a hapten, to the immunoglobulin E (IgE) on the surface of mast cells and basophils and maybe the cause of the few cases of anaphylactic shock that have been described. Other patients may be allergic to metabisulfite conservative, found in preparations containing adrenaline (epinephrine). 

Examples of widely used pharmaceutical preservatives include benzoic acid, benzyl alcohol, para hydroxybenzoates, 2 phenylethanol, phenyl mercuric nitrate. Whereas some have been known to suffer from absorption in certain plastics, others have been known to suffer from variable adsorption, which is far less predictable than absorption since it depends on the surface area involved. 

The structural formula shown is para-hydroxybenzoic acid, a weak diprotic acid used as a food preservative. Titration of 25.00 mL of a dilute aqueous solution of this acid requires 16.24 mL of 0.0200 M NaOH to reach the first equivalence point. The measured pH after the addition of 8.12 mL of the base is 4.57 after 16.24 mL, the pH is 7.02. Determine the values of pXaj and of para-hydroxybenzoic acid and the pH values for the two equivalence points in the titration. 

Related to salicylic acid as isomers are / -hydroxybenzoic acid [99-06-9] andy>-hydroxybenzoic acid [99-96-7]. The three are commonly known as the monohydroxybenzoic acids because of the shared chemical reactions, the three isomers are discussed together herein. These monohydroxybenzoic acids have a broad range of applications from paper coatings and liquid crystal preparations to drugs. Salicylic acid and its derivatives are interesting because of their demonstrated activity as analgesics, antipyretics, and antiinflammatory agents, whereas the para-substituted acids and esters known as parabens have activity as preservatives for food. 

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