The Solubilization Process

Studies of micelle formation indicate that surfactant properties such as the cmc and aggregation number can be reasonably well correlated with the size and nature of the hydrophobic group. Unfortunately, comparably convenient relationships are not always so apparent in terms of surfactant structure and solubihzing power, probably because the structure of the additive can play such an important role in the overall aggregation process. Nevertheless, many of the factors discussed previously that cause an increase in micelle size might also be expected to increase the solubilizing power of the system. 

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In addition to the degree of hydrophilicity of the solubilizates, their size and structure, the size of the host microregions, or the occurrence of specific processes must be taken into account in order to rationalize the driving forces of the solubilization process and of the solubilization site within water-containing reversed micelles [25,138,139],... 

When cell-wall fragments are incubated in molar NaCl, ionically bound proteins are released into the incubation medium. All investigated crude cell extracts deesterified Citrus pectin (Table 2) but the deesterification rates were clearly higher when the enzymes were still bound to the cell walls, indicating a major loss of activity during the solubilization process. 

Precipitation of compound from a DMSO stock is an issue of compound solubility in DMSO [14]. However, operationally, most organizations dissolving compounds in DMSO do not encounter problems in the solubilization process. This apparent paradox is explained by the issue of amorphous compounds. The vast majority of compounds solubilized into DMSO stocks are amorphous and inherently more soluble in DMSO (as previously discussed). The vast majority of the same compounds precipitating from DMSO are crystalline and much less soluble in DMSO (as previously discussed). The problem of compounds precipitating from DMSO occurs because so many compounds entering into screening libraries are amorphous. The precipitation of compounds from DMSO would be far less of a problem if screening compounds were entirely crystalline as they were 20 years ago. Quite simply DMSO insoluble crystalline compounds would never have been successfully dissolved in DMSO in the first place. 

One approach to the study of solubility is to evaluate the time dependence of the solubilization process, such as is conducted in the dissolution testing of dosage forms [70], In this work, the amount of drug substance that becomes dissolved per unit time under standard conditions is followed. Within the accepted model for pharmaceutical dissolution, the rate-limiting step is the transport of solute away from the interfacial layer at the dissolving solid into the bulk solution. To measure the intrinsic dissolution rate of a drug, the compound is normally compressed into a special die to a condition of zero porosity. The system is immersed into the solvent reservoir, and the concentration monitored as a function of time. Use of this procedure yields a dissolution rate parameter that is intrinsic to the compound under study and that is considered an important parameter in the preformulation process. A critical evaluation of the intrinsic dissolution methodology and interpretation is available [71]. 

Fluorescence quenching studies in micellar systems provide quantitative information not only on the aggregation number but also on counterion binding and on the effect of additives on the micellization process. The solubilizing process (partition coefficients between the aqueous phase and the micellar pseudo-phase, entry and exit rates of solutes) can also be characterized by fluorescence quenching. 

To increase the usefulness of bioremediation as an effective field remedial tool, significant investments have been made towards the development of means to remove sorbed PAHs, attack sources of NAPL, and subsequently increase the aqueous solubility/bioavailability, and thus the biodegradability, of targeted compounds. To date, one of the most effective ways to accomplish these tasks involves the use of surface active agents (i.e., surfactants). A variety of synthetic surfactants have been shown effective in increasing the bioavailability of PAHs and other hydrophobic contaminants (Kile Chiou, 1989, 1990 Edwards et al., 1991 Liu et al., 1991). Although the solubilization process is not completely understood, these studies showed that a variety of ionic and nonionic surfactants could significantly increase the water solubility of monitored chemicals. 

Gadelle et al. (1995) investigated the solubilization of various aromatic solutes irbfftRSS-b-PEO (ABA)/PPO-bPEO-bPPO (BAB) triblock copolymers. According to the experimental results, they indicated two different solubilization processes. To understand better the mechanism for solubilization in the polymeric surfactant solutions, it was postulated that (1) the addition of apolar solutes promotes micellization of the polymeric surfactant molecules, (2) the central core of the polymeric micelles contains some water molecules, and (3) solubilization is initially a replacement process in which water molecules are displaced from the micellar core bythesolubilizate. Adetailed discussion of the solubilization process can be found in the next section and the pharmaceutical application section of this chapter. 

Measurements of thermodynamic parameters can provide important information on the chemical nature of the solubilization process. The partial molar volumes of a hydrocarbon in a micellar solution is very similar to the value obtained for a hydrocarbon phase, and differs significantly from that obtained in water39,183. ... 

In order to achieve the above objectives, three vinyl acrylic latexes of varying butyl acrylate content have been prepared and cleaned1 for use in the study. Several anionic and nonionic surfactants commonly usod in emulsion polymerization have been used to investigate the effects of surfactant structure and polymer composition on the solubilization process. Polarity of latex surface estimated from contact angle measurements have been used to study the effect of polymer polarity on surfactant adsorption. 

The prediction of antiwear benefits and optimization of the ZDDP dosage has become a very complex task. The chemistry of the mode of action of ZDDP itself is complicated and so the nature of its interactions with other additives needs investigating all the more. Interaction between ZDDP and fatty acids, again in lubricating oil formulations, shows a considerable amount of mechanical test wear. The antiwear property of ZDDP is reduced by fatty acid additive due to the adsorbed layer of fatty acid, and the solubilization process, which disturbs the function of ZDDP (Otsubo, 1975), see Fig. 2.11. 

The actual solubilization limit depends on the temperature, the nature of surfactant, the concentration of water, and on the nature of the acid. Irrespective of size or the specific properties of the solubilized molecules, very little is known about the thermodynamics or the kinetics of the solubilization process. The association of the solute with the interface can be checked using techniques capable of yielding detailed microscopic information at the molecular level (e.g. NMR, ESR, fluorescence, hydrated electrons). 

Solubilization By reference to Figure 3.1, The soft-core RMs , explain the solubilization process of carboxylic acids, such as acetic acid and oleic acid by calcium phenolate RMs in engine oil. 

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). 

The initial descending leg is interpreted as the solubilization process. If micelles are present, the added oil will be solubilized. Also, the added oil may be solubilized in the hexadecyltrimethylammonium bromide-cetyl alcohol complex. That the sol-... 

Concerning aromatic solutes there is less agreement alx)ut the solubilization process. Data have been presented suggesting that, for example, benzene, is located in the micellar interior, in the palisade layer, or near the micellar surface, or indeed in aU these locations. ... 

The solubilization process seems to be well understood on a qualitative basis. Quantitatively, however, there appears to be less agreement. First, in reporting the extent of solubilization different authors may use different definitions and concentration units, as we discuss later. Second, for a three-component system both the concentrations of the surfactant and the solute can be varied. This means that we rarely find data that are directly comparable due to variation in concentrations. Often solubilization is reported as single points along the concentration profiles of surfactant and solute. In some cases the method of measurement sets the limits. 

The mass action model describes micelle formation as an equilibrium process. The micellar aggregation number becomes an important parameter. The solubilization process can be treated as a stepwise addition of solute molecules to the micelles. However, the partition coefficient based on this model requires the aggregation number, which makes it difficult to use in practice. There are several methods of simplification. One is to define the partition coefficient as ... 

Selective solubilization can also occur in mixtures of polar and nonpolar oils. Using their oil drop method described previously, Chen et al. measured solubilization rates of mixtures of triolein and oleic acid in solutions of pure nonionic surfactants. As Figure 9.9 shows for a drop initially containing 85/15 triolein/oleic acid by weight injected into 2 wt% Tergitol 15-S-7 at 35°C, they observed that the solubilization process consisted of two stages. In the first stage, the drop radius... 

Ultrasonic wave clearly enhances the solubilization process (Figure 7, 8). Figure 8 also indicates that diffusion-controlled dissolution maintained even under ultrasonic pulses. The diffusivity under ultrasonic pulses was measured to increase about 3-4 times at the given geometry and power used in this experiment. There are two known effects of ultrasonic waves on solubilization i) acoustic streaming, and ii) cavitation/implosion[24,25]. 

The goal of the present work was to investigate the molecular implications governing the solubilization process of TCC into the core of poloxamine polymeric micelles and the further understanding of the phenomena associated with the limited antibacterial performance of the drug. 

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