Methyl- and propylparaben

Although this chapter is directed toward ophthalmic products, it is largely applicable to parenteral and even nonsterile products (solutions, emulsions, and suspensions). The choice of preservative is limited to only a few chemicals that have been found, over the years, to be safe and effective for this purpose. These are benzalkonium chloride, thimerosal, methyl- and propylparaben, phenylethanol, chlorhexidine,... 

Methyl- and propylparaben These esters of p-hydroxybenzoic add have been used primarily to prevent growth of molds, but in higher concentrations possess some weak... 

In addition to the above-mentioned excipients and functions, preservation of formulations in multiple dose containers is also required. Therefore, antimicrobial preservatives such as phenol, methyl-, and propylparabens are added. Apart from their formulation function the excipients also interact specifically with the protein and can thereby cause alterations in its function and stability (7). For example, phenol has an influence on the stability and conformation of the insulin hexamer. The addition of phenol shifts the structure from the less stable T3 to the more stable R6 (71). 

A list of regulatory approved antimicrobial preservatives used in ophthalmic formulations with recommended concentration ranges is shown in Table 12.7. The use of methyl- and propylparabens, thimerosal and other mercurial preservatives has decreased in recent years due to adverse reactions associated with their use (Wade and Weller 1994). 

H 7.27%, O 24,71%. Prepn of analogous derivatives See ethyl -, methyl - and propylparaben. Prepn of cal -cium and magnesium salts Engels, Wedjlard, U.S. pats. 

EMA (2013) Reflection paper on the use of methyl- and propylparaben as excipients in human medicinal products for oral use. http //www.ema.europa.eu/docs/en GB/document library/Sci entific guideline/2013/05/WC500143139.pdf... 

Microbial Considerations Merquat polymers are preserved with methyl- and propylparabens. Conditioner P7 does not support or inhibit microbial growth... 

Microbial Considerations Merquat 280 is preserved with methyl- and propylparabens Special Comments Highly substantive to skin and hair Supplier Calgon... 

Microbial Considerations Preserved with methyl- and propylparabens... 

Eisenach JC, et al. Phase I human safety assessment of intrathecal neostigmine containing methyl-and propylparabens. Anesth Analg 1997 85 ... 

Each gram of Plexion (sodium sulfacetamide 10% and sulfur 5%) cleanser contains 100 mg sodium sulfacetamide and 50 mg sulfur in a cleanser base containing water, sodium methyl oleyltaurate, sodium cocoyl isethionate, disodium oleamido MEA sulfosuccinate, cetyl alcohol, glyceryl stearate and PEG-100 stearate, stearyl alcohol, PEG-55 propylene glycol oleate, magnesium aluminum silicate, methylparaben, disodium EDTA, butylated hydroxytoluene, sodium thiosulfate, fragrance, xanthan gum, and propylparaben. Each gram of Plexion (sodium... 

Aqua, glycerin, cyclopentasiloxane, ascorbic acid, propylene glycol, nylon-12, sodium citrate, dimethicone copolyol, acrylates copolymer, disodium EDTA, methyl paraben, propylparaben and parfum. 

Parabens (methyl-, ethyl-, BUTYL-, AND PROPYLPARABEN) As a group, parabens are the most widely used cosmetic preservatives. They were banned in European cosmetics but are still allowed by the FDA. There is growing evidence that they mimic estrogen, which disrupts hormonal activity. A recent finding of high levels of parabens in breast tumors has spurred U.S. consumer protection groups to lobby the FDA against their use. 

Systemically, no adverse reactions to parabens have been reported, although they have been associated with hypersensitivity reactions. Parabens, in vivo, have also been reported to exhibit estrogenic responses in fish. " ° The WHO has set an estimated total acceptable daily intake for methyl- ethyl-, and propylparabens at up to lOmg/kg body-weight. " " ... 

The WHO has set an estimated total acceptable daily intake for methyl-, ethyl-, and propylparabens at up to lOmg/kg body-weight. ... 

Minoxidil and tretinoin were extracted from cosmetic formulations and separated from methyl-, ethyl-, and propylparabens on a cyanopropyl column (A = 283 nm and 367 nm). A 30-min 10/90 ->-70/30 acetonitrile/water (10 mM NaC104 to pH 3 with HCIO4) gradient was used. Calibration curves were generated for 1-500 pg/mL samples. Detection limits of 5ng were reported [1540]. 

Formulation sterile, non-pyrogenic injectable solution in water containing sodium citrate hydrous, citric acid anhydrous, sodium metabisulfite, methyl-paraben and propylparaben. pH is adjusted with hydrochloric acid or sodium hydroxide. Supplied as ampoules or bottles, concentration 10 mg/mL, 20 mg/mL. 

Online solid-phase extraction coupled to flow injection analysis-micellar electro-kinetic chromatography (MEKC) was used to concentrate the parabens and remove the matrix components. The breakthrough volume with three parabens solutions at 50 pg/ mL was found to be 2.0 mL. Moreover, the enrichment factors obtained for methyl-paraben, ethylparaben, and propylparaben were 65, 68, and 72, respectively, compared with flow injection analysis MEKC without solid-phase extraction. Furthermore, matrix effects were not observed because the technique was highly selective (Table 10.1) [12]. Thus, the method could be successfully used to extract parabens in water-based lotions, oil-based lotions, gels, and creams. 

Additional interactions between silica and neutral and acidic analytes have been observed [3,317,321]. One example is the resolution of methyl-paraben from propylparaben, benzoic acid, and famotidine [3]. Retention mechanism studies appear to show that interactions with the siloxane bridges are important [322]. 

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