Parahydroxybenzoic acid esters

Patel N, Kostenbauder HB. Interaction of preservatives with macromolecules I binding of parahydroxybenzoic acid esters by polyoxyethylene 20 sorbitan monooleate (Tween 80). J Am Pharm Assoc (Sci) 1958 47 289-293. 

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,... 

The relationship between concentration and activity differs greatly for the different preservatives and is rarely linear. The doubling of concentration does not necessarily lead to the doubling of activity. Increasing the concentration of phenylmercuric borate in eye drops from 0.002 % to 0.004 % for instance causes no better functioning [51]. In contrast, halving the concentration parahydroxybenzoic acid esters causes a roughly tenfold reduction of the activity. 

The parahydroxybenzoic acid esters can also be classified as phenols, but they are separately discussed in Sect. 23.8.6. 

An oral suspension of chlorpromazine has the following composition and must be extracted so that excipients are removed prior to analysis by UV spectrophotometry Chlorpromazine 0.025% w/v, parahydroxybenzoic acid methyl ester 0.1 % w/v, neutral water soluble dye, lipophilic flavouring agent, sodium lactate buffer. 

The majority of preservatives are bacteriostatic rather than bacteriocidal, and consist of both acid and nonacid types. Among the acidic types are phenol, chloro-cresol, O-phenyl phenol, alkyl esters of parahydroxybenzoic acid, benzoic acid, boric acid, and sorbic acid, and their respective salts. Therefore, the pH of solution, and the pAa of the preservative need to be carefully evaluated prior to selecting a preservative for a formulation. Neutral preservatives include chlorobutanol, benzyl alcohol, and beta-phenylethyl alcohol. Under alkaline conditions, it is generally regarded that most microbial growth is significantly retarded at these pH values, which reduces the need for a preservative. 

CAS 4247-02-3 EINECS/ELINCS 224-208-8 Synonyms 4-Hydroxybenzoic acid, 2-methyl propyl ester Isobutyl 4-hydroxybenzoate Isobutyl p-hydroxybenzoate Isobutyl parahydroxybenzoate Definition Ester of isobutyl alcohol and p-hydroxybenzoic acid Empirical C11H14O3 Properties M.w. 194.25... 

Hydroxybenzoic acid esters Methyl parahydroxybenzoate 1-1.5 mg/mL or mg/g, in combination with propyl hydroxybenzoate 0.5-0.6 mg/mL or mg/g Stability optimum pH 3-5 better activity in acid environment (pH < 8) Allergic reactions... 

Methyl parahydroxybenzoate (Fig. 23.15) or methyl-paraben is the most common representative of the hydroxybenzoic acid esters. 

Membrane Active—Protonophores Weak organics acids, parabens (parahydroxybenzoates and esters of parahydroxy-benzoic acid). 

These additives are commonly referred to as preservatives . They include additives such as sulphite nitrite sorbic acid and its salts benzoic and parahydroxybenzoic acids and their esters free chlorine and hypochlorite. They inhibit the growth of pathogenic bacteria in foods which have been contaminated and which, because of their composition, can support bacterial growth. 

AI3-02955 Benzoic acid, 4-hydroxy-, phenylmethyl ester Benzoic acid, p-hydroxy-, benzyl ester Benzyl 4-hydroxybenzoate Benzyl p-hydroxybenzoate Benzyl parahydroxybenzoate Benzyl Parasept Benzyl Tegosept Benzylparaben EINECS 202-311-9 Nipabenzyl NSC 8080 Parosept Phenylmethyl 4-hydroxybenzoate Solbrol Z. Among the most widely used preservatives in food, drugs, and cosmetics. Preservative, bactericide, fungicide for pharmaceuticals, cosmetics, foods, medicinal preparations, industrial applications. Crystals mp = 110-112°. Nipa. 

CAS 94-13-3 EINECS/ELINCS 202-307-7 FEMA 2951 INS216 E216 Synonyms 4-Hydroxybenzoic acid, propyl ester p-Hydroxybenzoic acid, propyl ester p-Hydroxypropyl benzoate Propyl 4-hydroxybenzoate n-Propyl p-hydroxybenzoate Propyl p-hydroxybenzoate Propyl parahydroxybenzoate Propyl parasept Classification Organic ester Definition Ester of n-propyl alcohol and p-hydroxybenzoic acid Empirical C10H12O3... 

The solubility of active substances often depends on the pH (see Sect. 5.8.1). By adjusting the pH, a solution or a suspension may be prepared (see Sect. 19.1.1). The pH can affect the stability of an active substance or excipient. For example, the hydrolysis rate of esters depends on the pH (see Sect. 22.2.1). The pH must be taken into account for the preservation of an oral solution. The preservative sorbic acid is only effective at a pH <5.5 and the preservative methyl parahydroxybenzoate undergoes hydrolysis at pH > 8. 

Examples of substances that are prone to hydrolysis are acetylsalicylic acid, ampicillin, barbiturates, chloramphenicol, chlordiazepoxide, cocaine, corticosteroid phosphate or succinate esters, proteins, folinic acid, indomethacin, local anaesthetics, paracetamol (acetaminophen), pilocarpine, tropa alkaloids (atropine, scopolamine), xylomethazoline and the antimicrobial preservatives methyl and propyl parahydroxybenzoate. In the field of oncology, melphalan and bendamustine hydrochloride are highly susceptable to hydrolysis with a shelf life of 1.5 h for melphalan and 3.5 h for bendamustine at room temperature. 

Hydroxybenzoie acid ethyl ester Carbethoxyphenol Ethyl parahydroxybenzoate Ethylparaben Nipagin A E 214 (sodium salt E 215). 

Propyl parasept 4-hydroxybenzoic acid propyl ester Propyl parahydroxybenzoate Propylparaben Nipasol M E 216 (sodium salt E 217). 

Synonyms 4-Hydroxybenzoic acid, methyl ester Methyl 4-hydroxybenzoale Methyl p-hydroxybenzoate Methyl p-ox enzoate Methyl parahydroxybenzoate ... 

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