Solutions benzethonium chloride

Benzethonium chloride 1%, water, amphoteric 2, aloe vera gel, DMDM hydantoin, citric acid. 

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Figure 7.37 Zeta potential of glass (powder) and chloramphenicol in aqueous benzethonium chloride solutions. Reproduced from H. Uno and S. Tanaka, Kolloid Z. Z. Polym., 250, 238 (1972).

Add to a 150-mL beaker a sample consisting of about 0.15 mmoles anionic surfactant in a volume of about 50 mL H2O. Titrate potentiometrically with benzethonium chloride solution at a rate of 0.5 mL/min until well past the inflection point of the curve. An automatic titrator with 5-mL buret assembly is used, equipped with a nitrate-selective electrode (HNU Systems model lSE-20-31-00, Orion model 93-07, or equivalent) and a Ag/AgCl reference electrode with ground-glass sleeve. 

Other quaternary ammonium germicides, ben-zethonium chloride and benzalkonium bromide, have been used in several ophthalmic solutions. While these have the advantage of not being a chemical mixture, they do not possess the bactericidal effectiveness of benzalkonium chloride and are subject to the same incompatibility limitations. In addition, the maximum concentration for benzethonium chloride is 0.01%. Several new products that form gels in the eye, like Timolol Gel Forming Solution and Timoptic-XE, employ another quaternary preservative, BDAB, in the formulation. 

Materials Required Benzethonium chloride 0.15 g Chloroform 50 ml bromophenol blue solution (Dissolve with heating 0.2 g of bromophenol blue in 3 ml of 0.1 M NaOH and 10 ml of ethanol (96%). Allow to cool and dilute to 100 ml with ethanol 96%] 50 ml sodium tetraphenyl borate solution (1% w/v in chloroform) 50 ml sintered-glass crucible No 4. 

VoSol Otic solution Acetic acid (2%) Propylene glycol (3%) Benzethonium chloride... 

VoSol HC Otic solution Hydrocortisone (1%) Acetic Propylene glycol Benzethonium chloride... 

Benzethonium chloride is stable. Aqueous solutions may be sterilized by autoclaving. 

Benzethonium chloride is incompatible with soaps and other anionic surfactants and may be precipitated from solutions greater than 2% w/v concentration by the addition of mineral acids and some salt solutions. 

The topical use of solutions containing greater than 5% w/v benzethonium chloride can cause irritation although benzethonium chloride is not regarded as a sensitizer. The use of 0.5% w/v benzethonium chloride in cosmetics is associated with few adverse effects. A maximum concentration of 0.02% w/v benzethonium chloride is recommended for use in cosmetics used in the eye area and this is also the maximum concentration generally used in pharmaceutical formulations such as injections and ophthalmic preparations. ... 

Benzethonium chloride (BEC) is supplied as a white crystalline, odorless material. Early in BEC s history, a methylated derivative, methylbenzethonium chloride, was also available, but it has all but disappeared from use in the last two decades. Both compounds are soluble in polar solvents such as water, low molecular weight alcohols, and glycols and also in nonpolar solvents such as carbon tetrachloride, tetrachloroethane, and benzene [8]. Aqueous solutions of benzethonium chloride are stable within a pH range of 4-7 [9-11]. BEC offers better detergency action than BAK and exhibits different antimicrobial activity. 

The CTFA Final Report on the Safety Assessment of benzethonium chloride, published in 1985, concludes that this QAC is safe at levels of 0.5% in cosmetic products applied to the skin [8]. It was noted that benzethonium chloride produced mild skin irritation at 5% but not at lower concentrations. The report also limits the maximum concentration of 0.02% of this ingredient for cosmetics used in the eye area. The FDA s tentative final monograph (21CFR333) for first aid antiseptics specifies that benzethonium chloride s safe and effective concentrations are 0.1-0.2% for these products [14]. Aqueous and alcohol solutions of benzethonium chloride are not absorbed through the skin [15]. Oral LD50 values of 368-654 mg/kg in rats have been reported [16], Benzethonium chloride has also been shown to be nonmutagenic in at least two different types of tests [17,18]. 

For example, suppose a sample of 0.5878 g of an anionic surfactant was dissolved in water and diluted to 250 ml, and that 10 ml of the solution was titrated with exactly 0.004 mol/1 benzethonium chloride. Suppose the sample had been prepared in such a way that it could be assumed to be 100% pure for all practical purposes, and that the titration volume was 16.7 ml. Then ... 

ISO 2869 [6] and ISO 2870 [7] deal with the determination of alkali-and acid-hydrolysable detergents respectively. ISO 2869 prescribes boiling 25 ml of a 0.003-0.005 M solution for 30 min with 5 ml of aqueous 10 M sodium hydroxide. ISO 2870 prescribes boiling a similar sample for 3h with 5 ml of aqueous 5M (490 g/1) sulphuric acid. In both cases the hydrolysed solution is neutralised and titrated with benzethonium chloride (see section 3.5). In the acid treatment, [H" ] is only 1.67 M, and this may be insufficient for complete hydrolysis of the more resistant titratable species. Both methods should be used where appropriate, but ISO 2870 may not be universally valid, and if it is used for products containing... 

Many different cationics, at concentrations ranging from 0.001 to 0.005 M, have been used in this version of the titration, but 0.004 M benzethonium chloride is now the preferred titrant. The indicator solutions are 0.04% bromophenol blue and 0.004% methylene blue. 

Always carry out one or more control titrations on a standard solution of sodium dodecyl sulphate or benzethonium chloride in each set of analyses. 

If necessary, confirm the completeness of the deionisation as follows. Dissolve the residue from step 8 in chloroform and dilute to volume in a volumetric flask. Test a portion of this solution for the presence of whatever ionic surfactant predominated in the sample, e.g. by adding water and acid mixed indicator and titrating with benzethonium chloride. If the nonionic matter is not completely free of ionic surfactants, repeat the analysis using twice as much resin. 

Alkene monosulphonates may be extracted as the sulphonic acids from strongly acid solution and determined by titration with alkali. Under these conditions the hydroxyalkane sulphonates are converted back to the sultones from which they were derived, and although these are also extracted, they are not titrated by alkali. Alternatively the alkene sulphonates in the extract may be titrated with benzethonium chloride. The hydroxyalkane sulphonates may be determined by alkaline hydrolysis followed either by measurement of the alkali consumed or by a second titration with benzethonium chloride. The following method is adapted from those of Ranky and Battaglini [20] and Martinsson and Nilsson [21]. The alkali used for hydrolysis of the sultones is alcoholic simply to prevent excessive foaming. 

Titrate 20 ml of this solution with 0.004 M benzethonium chloride according to ISO 2271. 

Titration with benzethonium chloride in acid solution measures the sulphonated ester plus the sulphonated carboxylic acid, only the sulphon-ate group of the latter being titrated. In alkaline solution the titration measures the sulphonated ester plus twice the sulphonated carboxylate, both the sulphonate and the carboxylate group being titrated. Alpha-sulphonated esters give poor potentiometric titration curves, and two-phase titration is strongly preferred. 

Pipette a second 20 ml portion into a titration vessel, add 10 ml 0.1 M sodium hydroxide, 1.0 ml 0.04% bromophenol blue solution and 25 ml chloroform, and titrate with 0.004 M benzethonium chloride until the... 

The analyst may wish to use both procedures, using the solutions obtained in the acid-base titrations for the benzethonium chloride titrations. 

Alternatively, the correction for esters can be done by titrating the hydrolysed and unhydrolysed samples with benzethonium chloride in alkaline solution. The bromophenol blue method is recommended. 

One mol of aspartate reacts with 1 mol of mono- or dialkylsulphosuccin-ate when the latter is titrated with benzethonium chloride in acid solution. One mol of aspartate consumes 1 mol of acid when titrated, and/or 2 mol of alkali during alkaline hydrolysis. 

All may be determined by two-phase or potentiometric titration with benzethonium chloride. Titration of sulphosuccinamates in acid solution measures the sulphonate group alone (but see section 5.13.3), and titration in alkaline medium measures the carboxylate group as well (cf. section 5.11.3). Sulphosuccinamates, possessing a carboxylate group, can also be determined by potentiometric acid-base titration. 

Soaps, sarcosinates and alkylether carboxylates (ethoxycarboxylates, polyethylene glycol monoesters) give poor curves in potentiometric titrations with benzethonium chloride, and ISO 2271 in alkaline solution does not always work very well for these compounds, particularly those of shorter chain length. The bromophenol blue method works well provided that the solution is distinctly alkaline it is necessary to add 5 ml 0.1 M sodium hydroxide before titrating. 

Fatty acids and acyl sarcosines may be extracted with petroleum or diethyl ether from an acidified aqueous solution if no other surfactants are present, or with petroleum ether from acidified 50% ethanol if they are. The extract is evaporated and the residue weighed. Alkylether carboxylic acids cannot be quantitatively extracted with petroleum ether. They can be extracted from aqueous solution with chloroform, but they are best determined by two-phase titration with benzethonium chloride in akaline solution (bromophenol blue method) or direct potentiometric acid-base titration. 

B. Titration with benzethonium chloride in alkaline solution. The solution must be at least 0.1 M in hydroxide ion. Potentiometric titration is preferred, and the bromophenol blue method is probably better than the mixed indicator procedure. The present author s limited experience suggests that WW amphoterics are titrated rather more successfully as cationics than as anionics. 

SW sulphobetaines are more like anionics than cationics, and can be titrated with benzethonium chloride in alkaline solution, by either two-phase or potentiometric procedures. They cannot be titrated with NaTPB. 

Anions of strong acids undergo titration with benzethonium chloride at all pHs. Anions of weak acids do so only in alkaline solution. 

Mixtures of amphoterics are not likely to be encountered, but a basic approach is outlined which will succeed in many cases. Acid-base titration is unlikely to be useful because of the presence of other weak acids and bases. The procedure therefore relies on titration with SDS and/or benzethonium chloride (BEC) and will not always be completely successful. In all cases, if two-phase titration fails, potentiometric titration is still likely to succeed. Acid solutions must be at least 0.1 M in H and alkaline solutions at least 0.1 M in OH . It may be possible to replace SDS with NaTPB in at least some cases. Sulphobetaines cannot be determined in the presence of other amphoterics without separation. 

Standard quat solution, 5 x 10 or 1 x 10 " M benzethonium chloride. Benzalkonium chloride of chain length 14 or 8-18 carbon atoms may also be used. 

Pitaro J, Mood Z, Daniel SJ. Ototoxicity of aluminum acetate/benzethonium chloride otic solution in the chinchilla animal model. Lar)mgo-scope2013 123(10) 2521-5. 

Borane pyridine complex 550 Organic Salts and Solutions 9-Aminoacridine hydrochloride Benzethonium chloride... 

About 200 mg surfactant is dissolved in 70 mL water in a 500-mL separatory funnel. To this are added 30 mL 20% sodium sulfate solution, 0.5 mL 2 M H2SO4, and 100 mL methylene chloride. A stoichiometric quantity (determined by a prior titration) of benzetho-nium chloride solution is added, and the separatory funnel is shaken 1 min. The methylene chloride phase is drawn off and the solvent is evaporated, leaving the benzethonium salt of the anionic. 

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