Polysorbates solubilization

Emulsions of fatty- and petroleum-based substances, both oils and waxes, of the o/w type are made by using blends of sorbitan fatty esters and their poly(oxyethylene) derivatives. Mixtures of poly(oxyethylene(20)) sorbitan monostearate (Polysorbate 60) and sorbitan monostearate are typical examples of blends used for lotions and creams. Both sorbitan fatty acid esters and their poly(oxyethylene) derivatives are particularly advantageous in cosmetic uses because of their very low skin irritant properties. Sorbitan fatty ester emulsifiers for w/o emulsions of mineral oil are used in hair preparations of both the lotion and cream type. Poly(oxyethylene(20)) sorbitan monolaurate is useflil in shampoo formulations (see Hairpreparations). Poly(oxyethylene) sorbitan surfactants are also used for solubilization of essential oils in the preparation of colognes and after-shave lotions. 

Polysorbate 80 is widely used as a nonionic surfactant in liquid pharmaceutical products such as inhalation, suspension, and nasal suspension products, due to its properties of solubilization, reduction of surface and interfacial tension, and wetting. Direct analysis of Polysorbate 80 is quite time consuming. Size-exclusion chromatography (SEC) has been reported [5] in which a mobile phase contained the surfactant at concentrations above the critical micelle concentration. Polysorbate 80 appeared as a very broad peak and coeluted with other peaks, which makes quantification in Nasonex impossible. 

Shihab et al. (1979) determined the effects of electrolytes on the solubility of furosemide in 5% polysorbate 80 solutions. It was found that the CMC of the surfactant decreased and the micellar volume increased in the presence of electrolytes (Table 12.6). All the electrolytes used increased the solubilizing power of the surfactant at the concentrations employed. 

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. 

Li, R, S. E. Tabibi, andS. H.Yalkowsky. 1999. Solubilization of ionized and un-ionized Flavopiridol by ethanol and polysorbate 201. Pharm. Sci88 507-509. 

Attwood, D., G. Ktistic, Y. McCormick, and M. J. Story. 1989. Solubilization of indomethacin by polysorbate 80 in mixed water-sorbitol solvents. Pharm. Pharmacol. 41 83-86. 

Tween 80 (also known as At-Plus 109 and Polysorbate 80) is a polyoxyethylene sorbitan monooleate and was obtained from Atlas Chemical Industries, Inc. This nonionic surfactant has an HLB (hydrophile-lipophile balance) of 15.0 and is used as an emulsifier, solubilizer, and dispersant. It was used without further purification at the 0.1% (w/v) level in partitioning and greenhouse herbicidal evaluations as described below. 

Synthetic surfactants Laureth-9 sodium lauryl sulphate polysorbate 20 and 80 PEG-8 laurate sorbitan laurate glyceryl monolaurate saponins (e.g., Quillaja saponins) membrane interaction extraction of membrane proteins and lipids solubilization of peptides... 

To act as solubilizing, wetting, or emulsifying agents such as Cremophor EL, sodium desoxy-cholate, Polysorbate 20 or 80, PEG 40 castor oil, PEG 60 castor oil, sodium dodecyl sulfate, lecithin, or egg yolk phospholipid. 

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. 

Sorbitan monooleate, polysorbate 80, and unsaturated polyglycolyzed glycerides (Labrafils) are components in the cyclosporin formulations Gengraf and Sandimmune. Bexarotene is a benzoic acid derivative, which is a selective activator of the retinoid X receptor indicated for the treatment of T-cell lymphoma, and is solubilized in a mixture of Polysorbate 20 and PEG 400 (in combination with povidone and BHA as an antioxidant) in 75 mg Targretin soft gelatin capsules. 

Polysorbate 80 is a surfactant commonly used in protein parenteral formulations to minimize denaturation at the air-water interface. Polysorbate 80 is also sometimes used in injectable solution formulations of small molecules for the purpose of solubility enhancement owing to micelle formation. Docetaxel, a first-line therapeutic to treat breast and small cell lung cancer, is practically insoluble in water and is solubilized in Taxotere to 40mg/ml in 100% polysorbate 80, and is diluted four-fold with the supplied diluent of 13% ethanol in water, then further diluted to 0.3-0.74mg/ml with saline or dextrose 5% prior to administration by rV infusion. The dose of Taxotere is up to 5 ml of polysorbate 80 per dose, representing the estimated maximum amount administered intravenously. 

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. ... 

In a subsequent work, the solubilization of this substance by pH control combined with co-solvents, surfactants, or complexing agents was investigated (Li et al. 1999). Control of the solution pH was effected in combination with various surfactants (polysorbates 20 and 80) or cyclodextrin complexing agents. It was determined that the theoretical model developed by the authors could be successfully used to characterize the effects of pH, pKa, complexation constants, micelle partition coefficients, or solubilizing power of cosolvents on the solubility of ionized and non-ionized compounds. 

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