Cetomacrogol 1000 surfactant

Non-ionic surfactants are used in formulations to solubilise drugs with poor water solubility these compounds consist in their simplest form of an alkyl group attached to a polyethylene glycol chain. Non-ionic surfactants are usually mixtures, e.g. Cetomacrogol 1000, which has the general formula ... 

This product is an aqueous solution of water-soluble vitamins with oily vitamin A palmitate and cholecalceferol solubilized in water using the surfactant system of Tween 80 and Cetomacrogol. This syrup is a solubilized oil surfactant system and is liable to heat and rate of mixing. The temperature of solution must not exceed 30°C at the time of final mixing. The final mixing must be in continuous manner without any interruption. For the preparation of oily phase, the container must be dry. 

Oil-in-water creams, for topical use, generally contain mixed emulsifiers/surfactants one of which is a water soluble surfactant with a high HLB, the other being an amphiphile, usually a long chain fatty alcohol (e.g., of chain length C14 to Cig) or acid (e.g., palmitic or stearic). The water soluble surfactant may be anionic (e.g., sodium lauryl sulphate), cationic (e.g., cetri-mide), or non-ionic (e.g., cetomacrogol. Tweens). 

At a concentration of 0.1 %, chlorocresol may be completely inactivated in the presence of nonionic surfactants, such as polysorbate 80. However, other studies have suggested an enhancement of antimicrobial properties in the presence of surfactants. Bactericidal activity is also reduced, due to binding, by cetomacrogol, methylcellulose, pectin, or cellulose derivatives. In emulsified or solubilized systems, chlorocresol readily partitions into the oil phase, particularly into vegetable oils and higher concentrations will be required for efficient preservation. ... 

The selection of the surfactant is mainly based on the compatibility with the active substance. Sodium lauryl sulfate is an anionic surfactant and therefore incompatible with cationic active substances. Cetomacrogol emulsifying wax BP is incompatible with high concentrations of phenolic substances due to an interaction of the phenolic group with the polyethylene glycol chains in the macrogol cetostearyl ether. It is compatible with acids, high concentrations of electrolytes and cations. 

Cremophor A25, a cetomacrogol, is a surfactant with hydrophilic character its contact angle values were measured in aqueous solution do not alter significantly above 0.2% concentration, in accordance with the dissolution characteristics of the embedded samples. 

Temperature increase generally causes a slight decrease in the extent of adsorption of ionic surfactants. The effect is not pronounced and is insignificant compared with the effects of electrolyte and pH. Adsorption of polyoxyethylated non-ionic surfactants on to Graphon has been reported to increase with increase in temperature [43]. This effect has been attributed to a decrease in the hydration of the polyoxyethylene chain. The opposite effect was, however, noted for the adsorption of cetomacrogol on griseofulvin [46]. 

The investigation of the effect of a second solubilizate on the solubilizing capacity of a surfactant for a particular compound has received little attention, despite the fact that the solubilization of mixtures of solubilizates often occurs in pharmaceutical preparations. Crooks and Brown [181] have reported the solubilization of several pairs of preservatives by the non-ionic surfactant, cetomacrogol. Their results indicate that the solubilities of preservatives solubilized as mixtures may differ substantially from those determined for the compounds individually. No clear pattern of behaviour has emerged. Fig. S.23a shows that increasing concentrations of benzoic acid produce an apparently linear increase in the amount of methyl parabens solubilized by cetomacrogol whilst with di-chloroxylenol the solubility initially decreases to a minimum and then rises again. 

The binding of series of phenols, cresols and xylenols to the non-ionic surfactant cetomacrogol 1000 can be described by a Langmuir adsorption isotherm [19]... 

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 6.25 Amount of surfactants (cetomacrogol and polysorbate 20) required to solubilize 1 % flavouring oils in water...

Recently, insulin absorption via the jejunum has been effected by administration of insulin-cetomacrogol solutions to diabetic rats [87]. Results presented in Table 7.5 are most likely to be due to a membrane effect rather than a surfactant-protecting effect on insulin degradation, as insulin administered h after cetomacrogol elicited a hypoglycaemic effect (see Section 7.4.2 below on rectal absorption). Sodium lauryl sulphate (0.75%) and sodium taurocholate (3.2 %) have been reported to cause an increase in the percentage of insulin absorbed from the ligated rat jejunal loop from 0.4% to 3.2% and 3.4%,... 

The uptake of hexylresorcinol by . coli in the presence and absence of cetomacrogol exhibits the same trend as the uptake of iodine from aqueous solution and surfactant mixtures, with a marked reduction in the presence of detergent [190] the rate of uptake is not affected. Beckett et al. [190] consider that the phenol-cetomacrogol complex probably prevents cell-wall penetration. The amount of hexylresorcinol bound per organism is less than the theoretical... 

Figure 8.14 Change of zeta-potential with concentration of surfactant for chlorobenzene globules in aqueous solutions of (I) cetomacrogol sulphate and (II) cetomacrogol. From Attwood and Florence [76] with permission.

Wax BP, Cetomacrogol Emulsifying Wax BP and Cetrimide Emulsifying Wax (BP) are ready prepared mixtures for extemporaneous use. When these or similar mixtures are used the resultant emulsions are mobile at low emulsifier concentrations and semi-solid at moderate concentrations (about 10% or less of the total weight of the emulsion). The process whereby the surfactant mixture imparts the semi-solid characteristics over a period of time has been termed self-bodying [92-94], the essential feature of which is the introduction of a significant elastic... 

The aim in pharmaceutical formulations will be to reduce rates of degradation by appropriate choice of surfactant system, and to avoid surfactants which catalyse reactions. Cetomacrogol 1000 reduces the rate of hydrolysis of aspirin in its unionized state but does not stabilize the ionized form of the drug. Above a pH of about 3 it seems that only drug in the aqueous phase undergoes hydrolysis, so considering the micellar solution as a two-phase system [131] one can write... 

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