Chloroxylenol solution

Solubilization has been used for many years in the formulation of phenolic antiseptic and disinfectant solutions. In the case of Cresol and Soap Solution (Lysol) and Chloroxylenol Solution B.P., soap micelles are used to solubilize the phenolic substances. The soap (anionic surfactant) is formed by reaction of potassium hydroxide with a suitable oil such as linseed oil (in Cresol and Soap Solution) or castor oil (in Chloroxylenol Solution). The solubilizing potential of surfactant solutions for hydrophobic species has also been exploited in the design of cholelitholytic solvents for gallstone dissolution with some limited success. 

Chloroxylenol, solution Chloroxylenol, technical grade Choline chloride, diluted... 

Many derivatives of phenol are now made by a synthetic process. Homologous series of substituted derivatives have been prepared and tested for antimicrobial activity. A combination of alkyl substitution and halogenation has produced useful derivatives including clorinated phenols which are constituents of a number of proprietary disinfectants. Two ofthe most widely used derivatives are/ -chloro-m-cresol (4-chloro-3-methylphenol, chlorocresol, Fig. 10.7C) which is mostly employed as a preservative at a concentration of 0.1%, and / -chloro-m-xylenol (4-chloro-3,5-dimethylphenol, chloroxylenol. Fig. 10.7C) which is used for skin disinfection, although less than formerly. Chloroxylenol is sparingly soluble in water and must be solubihzed, for example in a suitable soap solution in conjunction with terpineol or pine oil. Its antimicrobial capacity is weak and is reduced by the presence of organic matter. 

This is an antifungal solution for topical use containing 25% undecylenic acid and 3% chloroxylenol as its active... 

A subject who had ingested about 17 g of chloroxylenol in solution was admitted to hospital 30 minutes afterwards and recovered after intensive treatment (P. Joubert et al., Br. med. J., 1978,1, 890). 

A 10-day-old baby who was given a bath in a 25% solution of Dettol containing 1.2% chloroxylenol became dehydrated and developed diffuse erythema and vesicles, and afterwards exfoliative dermatitis (1). There was a good response to therapy with systemic glucocorticoids and supportive measures. 

Sensitization reactions may follow the prolonged application of strong solutions to the skin, although patch tests have shown that chlorocresol is not a primary irritant at concentrations up to 0.2%. Cross sensitization with the related preservative chloroxylenol has also been reported. " "" At concentrations of 0.005% w/v, chlorocresol has been shown to produce a reversible reduction in the ciliary movement of human nasal epithelial cells in vitro and at concentrations of 0.1% chlorocresol produces irreversible ciliostasis therefore it should be used with caution in nasal preparations. " However, a clinical study in asthma patients challenged with chlorocresol or saline concluded that preservative might be used safely in nebulizer solution. ... 

Chloroxylenol is stable at normal room temperature, but is volatile in steam. Contact with natural rubber should be avoided. Aqueous solutions of chloroxylenol are susceptible to microbial contamination and appropriate measures should be taken to prevent contamination during storage or dilution. Chloroxylenol should be stored in polyethylene, mild steel or stainless steel containers, which should be well-closed and kept in a cool, dry place. 

Phenolic compounds such as cresol, chloro-cresol, chloroxylenol and thymol are frequently solubilised with soap to form clear solutions which are widely used for disinfection. Solution of Chloroxylenol BP, for example, contains 5% w/v chloroxylenol with terpineol in an alcoholic soap solution. 

Lysol. This is a compound of saponated cresol (mixture of 0-, m- and p-cresol) solution, usually 50% in saponified linseed oil), and was once used extensively as a disinfectant for floors and operating theaters in hospitals, p-chloro-m-cresol is the suspected allergen. It is reported to produce immediate immunological contact reactions (Sing-gih et al. 1986 Kiec-Swierczynska 1995). The patch-test concentration is 1% pet. Allergic reactions are not uncommon. Cross-reactions between p-chloro-m-cresol and p-chloro-m-xylenol (chloroxylenol) are common. 

Figure 5.23 (a) The solubility of methyl paraben in 0.019 m cetomacrogol solutions at 25° C as a function of A—A dichloroxylenol and O—O benzoic acid concentration. Solid points indicate solutions saturated with respect to both methyl paraben and co-solute, (b) The influence of varying concentration of methyl paraben on the solubility of — propyl paraben and O—O chloroxylenol in solutions containing 0.019 m cetomacrogol at 25° C. Shaded points indicate systems saturated with respect to both solute and co-solute. From Crooks and Brown [181] with permission. 

The influence of increasing concentrations of methyl paraben on the solubilization of propyl paraben and chloroxylenol is shown in Fig. 5.23b. At low concentrations, the methyl ester produces a sharp increase in solubility of the propyl ester which reaches a maximum then declines. The solubility of chloroxylenol is dramatically reduced by the addition of methyl paraben. Cetomacrogol solutions saturated with methyl paraben will dissolve only 61 % of the chloroxylenol that can be solubilized in solutions free from the methyl ester. Several possible explanations of the differences in effect have been proposed. Where compounds are solubilized within similar micellar regions it is likely that the solubil zates will compete with each other for the solubilization site leading to a diminished solubility of each. In addition there is the possibility of a cosolubilization effect where one solubilizate causes structural alterations in the micelle so enchancing its capacity for another. The simultaneous operation of two such mutually antagonistic processes would explain the occurrence of maxima and minima in the solubility plots. 

Solutions of cresol with soap were early pharmaceutical examples of solubilized systems. Phenol itself is soluble in water to the extent of 7.7 % (w/v), but it has disadvantages the alternatives, cresol, chlorocresol, chloroxylenol, and thymol, are much less soluble in water, and their use as disinfectants has led to the need for formulation in surfactant solutions. 

Mitchell [50] has shown that the activity of chloroxylenol in water and in solutions of cetomacrogol 1000 is related to the degree of saturation of the system. A saturated solution of chloroxylenol in water was found to have the same bactericidal activity as saturated surfactant solutions containing up to 100 times as much chloroxylenol. It is thus apparent that the activity depends on the amount of the bactericide free in the aqueous phase the compound has apparently no action inside the micelles. Table 6.5 shows some of these results and should emphasize the importance of these factors in formulation. 

Table 6.5 Dependence of the death time of E, coli in chloroxylenol-cetomacrogol solutions on cetomacrogol concentration at 20° C at a constant chloroxylenol concentration of 1.5%...

The saturation ratio is the ratio of the amount of chloroxylenol present to its solubility in the solution. 

No interference was obtained from/>-hydroxybenzoic acid esters, phenol, chlorbutol, chlorocresol and chloroxylenol in concentrations at which these materials are used as fungistats, bactericides and bacteriostats in aqueous eye-drop and injection solutions. Phenylmercuric nitrate (0-002 per cent w/v) which is sometimes used in these preparations as a bactericide produced a small positive error. The extent of this error will depend on the sample size and the compound being determined, but when contained in the preparations examined was in the range +0-2 to -f-l 0 per cent. 

Other Cresol-type Disinfectants and Antiseptics. Various non-irritant germicides of low toxicity, and therefore particularly suitable for disinfecting the skin and for application to wounds, contain different amounts of chloroxylenol, dichloroxylenol, benzyl cresols, o-phenylphenol, chloro-benzylphenols, special narrow-range boiling fractions of coal tar distillates, etc. They are usually dissolved in a soap, such as castor oil soap, and essential oil solution as they are only sparingly soluble in water. The various phenol coefficient tests, and particularly the Chick-Martin test, are of value in standardising such preparations, but they are of little value in determining their practical efficacy as antiseptics. For such purposes, other more specific tests are required which are beyond the scope of this book. 

The official chlorinated compounds are chlorocresol, C7H7OCI, Mol. Wt. 142 6, chloroxylenol, CgHgOCl, Mol. Wt. 156 6, and dichloroxylenol, CgHgOCl2, Mol. Wt. 191 1. These solid phenols are only slowly steam-volatile, but may be extracted from the original product with ether in the presence of sodium carbonate. After re-extraction from the ether with caustic alkali and then with ether from the acidified solution (to free from unsaponified matter), the ether is evaporated and the residue dried in a desiccator. The phenols should be recrystallised from water before identifying by melting-point. 

Solution of Chloroxylenol, B,P. A 5 per cent solution of chloroxylenol in a mixture of terpineol, alcohol and castor oil soap. The chloroxylenol in this preparation can be determined by the above fusion method after evaporation of 5 ml of the sample to dryness with sodium hydroxide or colorimetrically by the 4-aminophenazone method. 

---