Barbiturates, solubilization

Ismail, A. A., M. W Gouda, and M. M. Motawi. 1970. Micellar solubilization of barbiturates. I. Solubilities of certain barbiturates in polysorbates of varying hydrophobic chain ledcJRtiarm. Sci. 59 220-224. 

Treiner, C., M. Nortz, C. Vaution, and F. Puisieux. 1988. Micellar solubilization in aqueous binary surfactant systems Barbituric acids in mixed anionjcnonionic or cationiGf nonionic mixturesJ. Coll. Interf. 

Materials that are solubilized in polyethylene glycol can be solubilized in the polyoxyethylene chains on the surface of a nonionic micelle. Ismail, Gouda, and Motawi found that the micellar partition coefficients of barbiturates in polysorbates 20, 40, 60, and 80 is a function of the solute substituents and is proportional to the octanol-water partition coefficient of the barbiturate. Similarly, Ikeda, Kato, and Tukamoto showed that the solubilization of alkyl barbiturates by polyoxyethylene lauryl ether is not dependent upon the number of carbons in the substituents. Since the different polysorbates contain different aliphatic groups, the rather small dependence of solubilization upon polysorbate number (i.e., upon alkyl chain length) suggests that the barbiturates are not solubilized primarily in the hydrocarbon portion of the micelle. Gouda, Ismail, and Motawi showed that the solubilization of barbiturates in polyoxyethylene stearates is proportional to the number of polyoxyethylene units in the surfactant. 

Figure shows electropherograms of a mixture of five barbiturate standards it can be observed that the addition of micelles in MEKC clearly resulted in a different separation mechanism, reflected in various changes in elution order, compared to CZE. The migration behavior in MEKC depends largely on the hydro-phobic interaction of the analytes with the micelles. Hydrophobic components are more solubilized in the micelles, resulting in a slower migration compared to less hydrophobic compounds. 

Hydrolysis was the accompanying reaction to the reduction of 5,5-diallylbarbituric acid with NaBH4309,364 and to the N-methylation of different barbiturates.363-367 The effects of different protecting agents and solubilizers on the stability of medicinal barbiturates also deserve close attention because of their pharmaceutical importance.335,368-375 The stability of barbiturates in frozen systems has also been investigated.327 376 377... 

Several authors have noted a relationship between the lipophilicity of the solubilizate, expressed as its partition coefficient between octanol and water, Pocianob its Saturation distribution between micelles and the aqueous phase. Rank-order correlations between the amount of substituted barbituric acid solubilized by polyoxyethylene stearates and their Poctanoi values have been reported by Ismail et al. [133]. Similarly the partition coefficients of several steroids between water and micelles of long-chain polyoxyethylene non-ionic surfactants have been correlated with their ether/water partition coefficients [145], Fig. 5.18 shows a linear relationship between the partition coefficient of a... 

The search for suitable solubilizers is made necessary in the case of the barbiturates by the fact that the soluble sodium salts are unstable and less>soluble forms have therefore to be used. The increases in solubility brought about by 1 to 2% solutions of polysorbates 20-80 are not startling more water-soluble derivatives show a smaller increment in solubility in surfactant solutions (see Table 5.7, Chapter 5). 

Until more is known of the molecular interactions of surfactants with membrane components and the factors controlling such interactions it will remain virtually impossible to predict which surfactants will be capable of enhancing permeability of membranes without causing damage. Careful choice of solubilizer both of appropriate structure and optimum concentration is obviously paramount. In experiments on goldfish the effects of polyoxyethylene non-ionic surfactants on the absorption of various barbiturates is dependent on the surfactant hydro-phobic and hydrophilic chain lengths and possibly also on the size of the... 

---