Location of solubilizate

The solubilization phenomenon in hydrocarbon surfactant solutions is defined as a lowering of the activity of any solubilizates. The location of solubilizates in micelles can be investigated using probe molecules which indicate the surrounding conditions. 

FIGURE 48.2 Simplified structure of a micelle with the different locations of solubilizate. 

One of the most important consequences of micellization from a pharmaceutical point of view is that micelles are capable of solubilizing drugs of limited water solubility (see Chapter 6). Considerable interest centres on the exact location of solubilizates within the micellar structure, as discussed in Chapter 5. 

The different location of polar and amphiphilic molecules within water-containing reversed micelles is depicted in Figure 6. Polar solutes, by increasing the micellar core matter of spherical micelles, induce an increase in the micellar radius, while amphiphilic molecules, being preferentially solubihzed in the water/surfactant interface and consequently increasing the interfacial surface, lead to a decrease in the miceUar radius [49,136,137], These effects can easily be embodied in Eqs. (3) and (4), aUowing a quantitative evaluation of the mean micellar radius and number density of reversed miceUes in the presence of polar and amphiphilic solubilizates. Moreover it must be pointed out that, as a function of the specific distribution law of the solubihzate molecules and on a time scale shorter than that of the material exchange process, the system appears polydisperse and composed of empty and differently occupied reversed miceUes [136],... 

There is considerable interest in establishing the location within a micelle of the solubilized component. As we have seen, the environment changes from polar water to nonpolar hydrocarbon as we move radially toward the center of a micelle. While the detailed structure of the various zones is disputed, there is no doubt that this gradient of polarity exists. Accordingly, any experimental property that is sensitive to the molecular environment can be used to monitor the whereabouts of the solubilizate in the micelle. Spectroscopic measurements are ideally suited for determining the microenvironment of solubilizate molecules. This is the same principle used in Section 8.3, in which the ultraviolet spectrum of solubilized benzene was used to explore the solvation of micelles. Here we take the hydration for granted and use similar methods to locate the solubilizate. 

Although no quantitative description of the mechanism of solubilization is available, a knowledge of the location of the solubilizate in the micelle is necessary for an understanding of micellar catalysis. In the ensuing discussion, therefore, the attention will be focused on the possible locations of the different solubilizates in the molecular aggregates and on the experimental techniques used for determining this location. 

Adsorption chromatography and gel filtration techniques have also been utilized for quantitative measurements of the partitioning of solubilizates between the micellar phase and the bulk solvent (Kaufman, 1962 Herries et al., 1964 Dunlap and Cordes, 1968 Romsted and Cordes, 1968), but like distribution techniques these methods are completely ineffectual for elucidating the location of the solubilizate in the micellar phase. 

N.m.r. and e.s.r. techniques similar to those used for the determination of the location and environment of solubilizates in micellar systems have also been employed in investigations of solubilization by lipid micelles and of protein-substrate interactions (McDonald and Phillips, 1967 Meadows et al., 1967 Spotswood et al., 1967 Chapman, 1968 Penkett et al., 1968 Mildvan and Weiner, 1969 Raftery et al., 1969 Roberts et al., 1969a, b Rosenberg et al., 1969 Small et al., 1969). 

The location of a solubilized molecule in a micelle is determined primarily by the chemical structure of the solubilizate. Solubilization can occur at a number of different sites in a micelle ... 

A preferred location of the solubilizate molecule within the micelle is largely dictated by chemical structure. However, solubilized systems are dynamic and the location of molecules within the micelle changes rapidly with time. Solubilization in surfactant aqueous systems above the critical micelle concentration offers one pathway for the formulation of poorly soluble drugs. From a quantitative point of view, the solubilization process above the CMC may be considered to involve a simple partition phenomenon between an aqueous and a micellar phase. Thus the relationship between surfactant concentration Cm and drug solubility Ctot is given by Eq. (3). 

Predict the locations of the following solubilizates in a micelle of Ci2H25S04Na in aqueous medium ... 

Data obtained by this technique allow rather detailed conclusions about the location of the solubilizate in the aggregate. Fluorescence quenching rate constants vary with temperature, local microviscosity and quencher concentration. Encapsulation of spin probes has been examined in detail by EPR spectroscopy. ... 

Both models fail to precisely locate the solubilizate molecules within the micelles which can evidently influence the rate constant of the reactions and interfacial exchange of the solubilizates. 

The site of incorporation of solubilizate is closely related to its chemical structure (see Fig. 2.15). Although in many cases a particular location is preferred, the lifetime of a solubilizate within the micelle is long enough for a rapid interchange between different locations. 

Plots of (S /CpEo) versus (Cr/Creo) give straight lines from which a and b can be determined. This allows one to obtain the relative incorporation of solubilizate in the R and PEO chains. Several quantitative methods have been applied to obtain the exact location of the solubilizate ... 

NMR methods. NMR can be used to obtain information on solubilization by measuring the shift in the peak positions on addition of the solubilizate. For example, by measuring IH NMR shift for a compound with an aromatic ring versus the concentration of a surfactant that contains no aromatic ring, e.g. SDS, one can determine the location of the solubilizate. This leads to an upheld shift of the IH peak, indicating a more hydrophobic environment. 

The location of free radical solubilizates within the micelle has been determined from electron spin resonance (e.s.r.) spectra. As discussed in Chapter 3, these solubilizates can provide information on the nature of the various microenvironments of the micelle. Several workers have used nitroxide spin probes, the spectra of which are characterized by three sharp lines produced by nitrogen hyperfine interaction (Fig. 5.14). The distance between the resonance lines is determined by the hyperfine coupling constant, and this provides a sensitive... 

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