Small hydrophilic-lipophilic balance

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 other components of the carrier include surfactants and disinte-grants. Surfactants with a hydrophile-lipophile balance (HLB) value between about 10 and 25 are preferred. In some cases, the carrier is completely eliminated or added in small quantities to facilitate rapid release of the drug (Table 7.3). 

An emulsifier system must cause the concentrate to disperse spontaneously into small, stable droplets when mixed with water. To accomplish this, the surfactant system must have a most favorable solubility relationship a proper balance between oil and water solubility or, in other words, a favorable hydrophile-lipophile balance in solubility. This balance in solubility is frequently referred to as HLB and was first described by Griffin (6). However, the HLB system is based on the structure of a surfactant molecule and, therefore, predicts the behavior of a single molecule. It does not take into account tr 3 fact that many surfactants form micelles in organic solutions. If a micelle is formed, its HLB may have no relationship to the HLB of the monomer unit. Therefore, to select an emulsifier well, we will need a better understanding of the behavior of surfactants in organic solvents. 

M.D. Carson, D.J. "The Use of Hydrophilic Lipophilic Balanced (HLB) Copolymer SPE Cartridges for the Extraction of Diclofenac from Small Volume Pediatric Plasma Samples, J. Pharm. Biomed. Anal. 25, 871-879 (2001). 

TABLE 10.2 Some Small-Molecule Surfactants and Their Hydrophile-Lipophile Balance (HLB) Values... 

The number of different emulsifiers is in the thousands. Even restricting selection to nonylphenol ethoxylates leaves many choices. Some parameter is necessary to compare emulsifiers. Hydrophilic/Lipophilic balance (HLB number) was developed by W.C. Griffin (Griffin, 1949, 1954) in the 40 s and describes emulsifying properties of a surfactant. Values vary between 0 and 20. A low HLB, such as 4, indicates an oil soluble emulsifier useful for dissolving small amounts of water into oil. A large number, such as 16, indicates a water soluble emulsifier useful for dissolving small amounts of oil into water. The HLB number can be determined experimentally or calculated for alkyl and aryl ethoxylates from Equation 1. 

The cosurfactant molecules are polar enough to be surface active and reside between the tails of the surfactants, thereby increasing the buUdness of the tail group region. Cosurfactants have widely different hydrocarbon moiety sizes compared with the surfactants. Typical examples of cosurfactants are medium-chain alcohols, acids, and amines. The role of a cosurfactant is to (1) lower the interfacial tension down to a very small (near zero) value and increase the fluidity, (2) adjust the hydrophile-lipophile balance (HLB) and spontaneous curvature of the interface by controlling surfactant partitioning, (3) destroy the liquid crystalline and/or gel structures, and (4)... 

Specifically, polyprenyl phosphate vesicles form easily, provided that their lipophilic balance (the ratio of the lipophilic part to the hydrophilic part) is adequate. Single-chain polyprenyl phosphates require at least 20 carbons (geranylgeranyl, phytyl, or phytanyl phosphates). Double-chain polyprenyl phosphates require at least two C15 (famesyl) chains to generate vesicles, although this sometimes requires the help of a small amount of the corresponding free polyprenol (Pozzi et al., 1996) (see Figure 19.7.)... 

In microemulsions, oil and water mix over small length scales, and thus an extraordinarily large interfacial area spans the oil and water domains. In order to thermodynamically stabilize such fine structures, the surfactant must generate an ultra-low free energy per unit of interfacial area between oil and water microdomains within the microemulsion phase. Such low free energies result from a precise balancing of the hydrophilic-lipophilic nature of the surfactant. As a consequence of this precise balancing, the macroscopic interfacial tensions between microemulsion phases and excess oil phases are also ultra-low (of the order of 10-3 mN/m) (15, 16). 

While most lipophilic and large molecules are primarily excreted by the hepatobiliary system, the kidney is the major excretory organ for many small organic and inorganic molecules, drugs and hydrophilic metabolites, maintenance of fluid balance, and bone metabolism. These functions expose the kidney to a number of clinical, physiological, and pathological conditions that may compromise renal function. Some renal disorders that necessitate clinical intervention are listed in Table 2. 

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