Methyl parahydroxybenzoate

Reminyl is available as a 4 mg/mL galantamine hydrobromide oral solution. The inactive ingredients for this solution are methyl parahydroxybenzoate, propyl... 

Synonyms. Metagin Methyl Parahydroxybenzoate Methylis Oxybenzoas Methylparaben. 

METHYL-3-OXY-7-PYRONE see MAO350 METHYLPARABEN (FCC) see HJL500 METHYL PARAHYDROXYBENZOATE see HJL500 METHYL PAK SEPT see HJL500... 

BP Methyl hydroxybenzoate JP Methyl parahydroxybenzoate PhEur Methylis parahydroxybenzoas USPNF Methylparaben... 

To highlight the method development plan, we will look at a series of preservatives known as parabens. These preservatives are used in the cosmetic, pharmaceutical, and food industries and are effective antifungal and antimicrobial agents. Antifungal and antimicrobial activity increases with increasing chain length. Methyl and propyl parabens can be added directly to foodstuffs in most countries, and ethyl paraben is permitted in some countries. They can be incorporated into foods at a maximum level of 0.1%. Parabens do occur naturally, but those used in industry are synthetic analytes produced by the esterification of parahydroxbenzoic acid with a suitable alcohol. For example, methanol would be used in the manufacture of methyl parahydroxybenzoate. We have chosen to look at a subsection of the paraben series that includes... 

Methylparaben sodium Methylparaben sodium salt. See Sodium methylparaben 8-Methylparacymene. See p-t-Butyl toluene Methylparafynol. See Methyl pentynol Methyl parahydroxybenzoate Methyi Parasept NF/FCC, Methyl parasept. See Methylparaben Methyl parathion. See Parathion-methyl Methyl pelargonate... 

Hydrochlorothiazide Citric acid monohydrate Disodium phosphate dodeeahydrate Orange essence (local standard) Methyl parahydroxybenzoate Syrup BP (preserved with methyl parahydroxybenzoate 1 mg per g) Water, purified... 

Aluminium magnesium silicate Carmellose sodium M Citric acid monohydrate Methyl parahydroxybenzoate Raspberry essence (local standard) Sodium citrate... 

Syrup BP (preserved with methyl parahydroxybenzoate 1 mg per g) Water, purified... 

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. 

The pH of antacid suspensions is between 7.7 and 8.2. This pH range is very unfavourable for the stability and effectiveness of methyl parahydroxybenzoate and no other preservatives are available for that pH range. Propyl parahydroxybenzoate can be added but additional measures are needed to achieve a reasonable shelf life the use of raw materials with a low bioburden, preventing contamination during preparation, storage in the fridge, small bottles, limited usage period. 

Methyl parahydroxybenzoate (MOB or methylparaben) is most widely used in oral liquids. As an ester it is stable between pH 3 and 6. Outside these pH liinits methylparaben will hydrolyse, which amounts for example to 25 % in 12 months in an oral solution with pH 7.0-7.5 (prednisolone oral solution, see Table 23.23) at room temperature. 

Co-solvents such as ethanol, sugars, polyols, propylene glycol and glycerol, also have preservative properties if they are present in sufficient concentration (see also Sect. 23.3). Propylene glycol at 15 % is not quite as effective as sorbic acid or methyl parahydroxybenzoate and tastes unpleasant. Glycerol 85 % in concentration 30 % preserves less well than propylene glycol but tastes slightly sweet. 

Sucrose (present in syrups, see Sect. 23.4.4) preserves in concentrations above 63 % m/v. Usually symps contain 0.1-0.15 % methyl parahydroxybenzoate. 

Dissolve the methyl parahydroxybenzoate in 600 mL purified water while heating to 100 °C... 

Disperse the colloidal aluminium magnesium silicate in the hot solution of methyl parahydroxybenzoate... 

Methyl parahydroxybenzoate and propyl parahydroxybenzoate may cause an itching sensation on the tongue in some people. 

In general methyl parahydroxybenzoate (sometimes combined with propyl parahydroxybenzoate) or sorbic acid are chosen. For stability reasons the pH is adjusted to 5 by the addition of potassium sorbate. If these substances caimot be used, the organic solvents mentioned earlier (ethanol or glycerine) are an alternative to a preparation less susceptible to microbial growth. 

The ciliotoxicity of some substances depends on the pH of the solution. For instance when benzalkonium chloride is used as preservative, the pH of the preparation should be >5 to reduce the ciliotoxicity. Preservative efficacy can also be dependent on pH of the formulation. For instance, antimicrobial activity of benzalkonium chloride occurs between pH 4 and 10, and methyl parahydroxybenzoate exhibits antimicrobial activity over the pH range of 4-8 [38, 39]. See also Sect. 23.8.2. 

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