The Hydrophile-Lipophile Balance

The use of the HLB system can be illustrated as follows. Suppose that a certain 

Milky dispersion stable Translucent to clear solution 

The phase-inversion temperature (PIT) is defined as the temperature where, on heating, an oil—water—emulsifier mixture inverts from O/W to a W/O emulsion [23]. The PIT correlates very well with the HLB as illustrated in Fig. XIV-10 [72, 73]. The PIT can thus be used as a guide in emulsifier selection. 

The HLB system has made it possible to organize a great deal of rather messy information and to plan fairly efficient systematic approaches to the optimiza-tion of emulsion preparation. If pursued too far, however, the system tends to lose itself in complexities [74]. It is not surprising that HLB numbers are not really additive their effective value depends on what particular oil phase is involved and the emulsion depends on volume fraction. Finally, the host of physical characteristics needed to describe an emulsion cannot be encapsulated by a single HLB number (note Ref. 75). 

A beautiful and elegant example of the intricacies of surface science is the formation of transparent, thermodynamically stable microemulsions. Discovered about 50 years ago by Winsor [76] and characterized by Schulman [77, 78], microemulsions display a variety of useful and interesting properties that have generated much interest in the past decade. Early formulations, still under study today, involve the use of a long-chain alcohol as a cosurfactant to stabilize oil droplets 10-50 nm in diameter. Although transparent to the naked eye, microemulsions are readily characterized by a variety of scattering, microscopic, and spectroscopic techniques, described below. 

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Emulsifiers are classified by the hydrophilic—lipophilic balance (HLB) system. This system indicates whether an emulsifier is more soluble in water or oil, and for which type of emulsion (water-in-oil or oil-in-water) it is best suited. Emulsifiers having alow HLB value are more oil soluble, and are better suited for water-in-oil appHcations such as margarine. Conversely, emulsifiers having a high HLB value are more water soluble, and function more effectively in oil-in-water emulsions such as ice cream (34). The use of this system is somewhat limited because the properties of emulsifiers are modified by the presence of other ingredients and different combinations of emulsifiers are needed to achieve a desired effect. The HLB values of some common emulsifiers are given (35). 

One of the most important characteristics of the emulsifier is its CMC, which is defined as the critical concentration value below which no micelle formation occurs. The critical micelle concentration of an emulsifier is determined by the structure and the number of hydrophilic and hydrophobic groups included in the emulsifier molecule. The hydrophile-lipophile balance (HLB) number is a good criterion for the selection of proper emulsifier. The HLB scale was developed by W. C. Griffin [46,47]. Based on his approach, the HLB number of an emulsifier can be calculated by dividing... 

Formation of emulsions of the oil-in-water or water-in-oil type depends mainly on the hydrophilic-lipophilic balance (HLB) of the emulsifier. Phosphate esters with their various molecular structures can be adjusted to nearly every HLB value desired. Therefore they are able to meet nearly all of demands in this field. 

Particularly useful is the physical classification of surfactants based on the hydrophile-lipophile balance (HLB) system [67,68] established by Griffin [69,70]. More than 50 years ago he introduced an empirical scale of HLB values for a variety of nonionic surfactants. Griffin s original concept defined HLB as the percentage (by weight) of the hydrophile divided by 5 to yield more manageable values ... 

A series of amphiphiles containing a polygalactosylated tris(hydroxymethyl) aminomethane (Tris) linked to a diacyl aspartic acid (31) were synthesized by Polidori and co-workers.88 These compounds had a peptidic spacer for control of the hydrophilic/lipophilic balance as well as providing intermolecu-lar hydrogen bonding. The mono- and digalactosylated (31a, 31b) derivatives... 

Lo Y-L (2003) Relationships between the hydrophilic-lipophilic balance values of pharmaceutical excipients and their multidrug resistance modulating effect in Caco-2 cells and rat intestines. J Control Release 90 37 -8... 

The ability of these chemicals to penetrate the cuticle, the cell membrane, move into the protoplast and distribute in the plant is to a large measure dependent upon the hydrophilic/ lipophilic balance, the steric configuration and its stalaility in or on the plant. Similarly, these same chemical and physical factors are critical for toxicity of the chemical to the fungus. 

The key-step of the synthesis of glycolipids, and more generally of amphiphilic carbohydrates, is the covalent coupling of a hydrophilic carbohydrate with a lipophilic compound. A hydrophilic or hydrophobic spacer may be inserted between them in order to control the hydrophilic-lipophilic balance (HLB). This modulation allows to obtain variously organized systems with the same polar head and apolar tail. 

Marzdall L (1977) The effect of alcohols on the hydrophilic-lipophilic balance of nonionic surfactants. J Colloid Interface Sci 60 570-573... 

Bourrel M, Chambu C (1983) The Rules for Achieving High Solubilization of Brine and OU by AmphiphUic Molecules. Soc Petrol Eng J 23 327-338 Kunieda H, Shinoda K (1985) Evaluation of the hydrophile-lipophile balance (HLB) of nonionic surfactants I. Multisurfactant systems. J Colloid Interface Sci 107 107-121 Kahlweit M, Strey R, Eirman P (1986) Search for tricritical points in ternary systems Water-oil-nonionic amphiphile. J Phys Chem 90 671... 

The affinity of the polymer-bound catalyst for water and for organic solvent also depends upon the structure of the polymer backbone. Polystyrene is nonpolar and attracts good organic solvents, but without ionic, polyether, or other polar sites, it is completely inactive for catalysis of nucleophilic reactions. The polar sites are necessary to attract reactive anions. If the polymer is hydrophilic, as a dextran, its surface must be made less polar by functionalization with lipophilic groups to permit catalytic activity for most nucleophilic displacement reactions. The % RS and the chemical nature of the polymer backbone affect the hydrophilic/lipophilic balance. The polymer must be able to attract both the reactive anion and the organic substrate into its matrix to catalyze reactions between the two mutually insoluble species. Most polymer-supported phase transfer catalysts are used under conditions where both intrinsic reactivity and intraparticle diffusion affect the observed rates of reaction. The structural variables in the catalyst which control the hydrophilic/lipophilic balance affect both activity and diffusion, and it is often not possible to distinguish clearly between these rate limiting phenomena by variation of active site structure, polymer backbone structure, or % RS. 

Molecules consisting of a long hydrophobic part and one or two hydrophilic headgroups. Able to form micelles and/or liposomes depending on the hydrophilic-lipophilic balance (HLB). 

At low temperature, nonionic surfactants are water-soluble but at high temperatures the surfactant s solubility in water is extremely small. At some intermediate temperature, the hydrophile—lipophile balance (HLB) temperature (24) or the phase inversion temperature (PIT) (22), a third isotropic liquid phase (25), appears between the oil and the water (Fig. 11). The emulsification is done at this temperature and the emulsifier is selected in the following manner. Equal amounts of the oil and the aqueous phases with all the components of the formulation pre-added are mixed with 4% of the emulsifiers to be tested in a series of samples. For the case of an o/w emulsion, the samples are left thermostated at 55°C to separate. The emulsifiers giving separation into three layers are then used for emulsification in order to find which one gives the most stable emulsion. 

The hydrophilic-lipophilic balance (HLB) classi Lcation system was L rst introduced by GrifL n (1949) to characterize the relative afLnity of a surfactant to the aqueous and oil phase. A HLB value is an empirical numerical value in the range of 1-30. The higher the HLB value, the more hydrophilic the surfactant is and in turn, the lower the HLB value, the more lipophilic the surfactant is. As a result, surfactants with higher HLB values (>8) are favorable for formation of o/w emulsions, while surfactants with lower HLB values (3-6) are more suitable for the formation of w/o emulsions. The HLB values of the surfactants used in parenteral emulsions are listed in Table 10.2. 

In certain cases, cholesterol is required for vesicle formation. It is commonly accepted that the hydrophilic lipophilic balance (HLB) is a parameter that could indicate the vesicleforming potential of surfactants. For amphiphils such as sorbitan esters and alkyl ethers, low HLB values could predict vesicle formation [52,55]. However, niosomes were obtained from polysorbate 20 (HLB 16.7), a highly hydrophilic molecule, when cholesterol at an appropriate concentration was added to the amphiphil [44], In this case it could be assumed that a kind of amphiphilic complex with a lower HLB was responsible for the vesicle formation. An excellent review on the structure, characteristics, chemical composition, and mechanism of action of niosomes was published by Uchegbu and Vyas [41]. 

K. Shinoda and H. Takeda, The effect of added salts in water on the hydrophile-lipophile balance of nonionic surfactants the effect of added salts on the phase inversion temperature of emulsions, J. Colloid Interface Sci. 32 (1970) 642-646. 

Polyoxyethylene (POE) (20) sorbitan monooleate (Tween 80, Lot 36218, ICI Surfactants, Inc.) was used as received with no further purification. The average molecular weight of Tween 80 is 1310 g/mole, the density is 1.07 g/cm3, the hydrophile-lipophile balance (HLB) is 15, the critical micelle... 

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