Solubilization compounds

Molecules that possess both hydrophilic and hydrophobic structures may associate in aqueous media to form dynamic aggregates, commonly known as micelles. The properties of micellar structures have been discussed in great detail [66-69], but thejr main pharmaceutical application lies in their ability to provide enhanced solubility to compounds lacking sufficient aqueous solubility [70], The ability of a micelle to solubilize compounds of limited aqueous solubility can be understood from consideration of the schematic drawing of Fig. 10a. Above the critical micelle concentration, these molecules orient themselves with the polar ends in interfacing with the aqueous solution and the nonpolar ends at the interior. A hydrophobic core is formed at the interior of the micelle, and hydrophobic solute molecules enter and occupy this region. 

Another study found that 5% Tween 80 and HP-(3-CD were effective as solubilizing compounds with poor aqueous solubility without causing an increase in the transepithe-lial permeability of the monolayer integrity marker mannitol. The effect of these excipients on the biochemical integrity of the cells was not reported. 

Soaps and detergents make water wetter by lowering the surface tension of the water. In doing so, less energy is required to lift dirt off whatever it is on. Other agents within a cleaning solution may include materials that help emulsify oily matter, soften water, solubilize compounds, control pH, and perform other actions to assist the cleaning process. 

Similar approaches to enhance solubility have been studied in the PAMPA system. For instance, Kansy et al. (2001) explored the use of glycocholic acid to solubilize compounds. As PAMPA is a completely artificial system, it is expected that, compared to cell-based models, higher concentrations of cosolvents can be used. Sugano and coworkers reported that DMSO, ethanol and PEG 400 could be used up to 30% without causing disruptions of the lipid layer (Sugano et al., 2001). An effect of these cosolvents on the physicochemical properties of the test compounds (e.g. impact on pKa) may however lead to an unpredictable effect on drug permeability (Sugano et al., 2001). Currently, DMSO is commonly used as a cosolvent in the PAMPA system at a concentration of 1 to 2%. 

Despite its ability to remove much of the soluble plutonium present in body fluids, DTPA is not an exceptional chelating agent for tetravalent actinides. The formation constant of its plutonium complex is too low to displace hydroxides from the colloids and polymers of hydrolyzed plutonium or solubilize compounds such asPuC>2 at physiological pH. In addition, the inability of DTPA to completely coordinate the... 

One of the most relevant properties of aqueous micelles is their ability to solubilize compounds whose water solubility is limited. Because the size of the hydrophobic core of micelle is about 15 — 30 A, this solubilization process allows the organization of solutes on a molecular scaie. Hazardous materials solubilzed by micelles undergo similar processes as those of the surfactant monomers, i.e. rapid exchange takes place between micelles and the bulk solution. The solute, on the average, may spend most of its time within a micelle, with residence times approaching 10 3 sec being reported. Water penetration of two to four carbon atoms from the head group or surface of the micelle is often cited (Thomas J.K., 1980). 

F igure 2.11. This figure shows some of the eomponents within the Haystack compound storage and retrieval system (a) the microtiter plate handling system, (b) the solid storage system and the robot that handles the compound vials, and (c) the tube picking robot placing a solubilized compound back into a tube rack. 

Organic molecules with limited water solubility were solubilized by those poly soaps for which viscosity studies indicated micellar behavior (6). The solubilization had varied effects on the viscosity of the polysoap solutions, depending on the nature of the solubilized compound and the concentration... 

Pure DMSO has a melting point of 18.4°C at normal atmospheric pressure. DMSO-solubilized compounds are often stored at or below 4°C in a frozen form to prolong their shelf life beyond a few months (e.g., 6-9... 

TMS (Figure 19.12) is an example of a solubilized compound or a solubilizate , i.e. a compound which becomes soluble due to the presence of micelles. Typically, the solubility stays very low until the CMC is reached, while above the CMC it increases rapidly and almost linearly with the surfactant concentration (Figure 19.14). Solubilization is one of the most important phenomena for surfactant solutions, with a direct bearing on, inter alia, detergency and the formulation of pharmaceuticals. In order to study the solubilization equilibria, and thus obtain information on the thermodynamics of solubilization, the mentioned self-diffusion technique is the most general and useful approach. 

A big interest in micellar solutions is that these media are able to solubilize, at the same time, polar, ionic solutes and nonpolar solutes. The location of the solubilized compounds in the micelle or surroundings depends on the polarity of the solutes. On the other hand, when the amount of nonpolar solvent incorporated in a micellar phase becomes high, emulsion and... 

Due to the high cost of cell culture, Caco-2 assays are usually used as a follow-up to PAMPA in ADME screening [78], and as a result, the sample burden for bioanalysis is not as heavy as for some first-hne assays, such as metabolic stability. There have been a number of reports in the literature that use automated optimization and single LC-MS/MS for sample analysis for Caco-2 assay support [46,79-81]. Nevertheless, Caco-2 samples pose a unique bioanalytical challenge. Unlike plasma or microsomal samples rich in proteins that help solubilize compounds and prevent adsorptive loss, Caco-2 samples are essentially aqueous buffer samples with very little protein. As a result, compounds with low solubility and/ or adsorption problems tend to exhibit poor recoveries in the assay due to precipitation and adsorptive losses [82,83]. An effective solution to this problem is the use of organic solvent to catch compounds immediately after incubation, but prior to analysis, in order to maintain solubility and prevent adsorptive loss to container surfaces. Another approach involves the addition of some protein such as bovine serum albumin (BSA) to the assay buffer system, thus reducing compound loss/ precipitation and improving recoveries [84]. 

Naturally occurring alcohols or phenols often occur in cells combined as a glycoside with some sugar—most commonly, glucose. In this way, the many hydroxyl groups of the sugar portion of the glycoside solubilize compounds that would otherwise be... 

The half-height width (HHW) of the transition peak is used as a measure of the interactions between solubilized compounds and the phospholipid bilayers [130,133]. This is one of the few available methods for determining the amount of hydrophobic material incorporated into the liposomes. Fildes and Oliver [131] used this criterion to maximize the incorporation of hydrocortisone-21-palmitate in dipalmitoylphosphatidylcholine liposomes. The temperature of the main phase transition was considered independent of steroid content, although the HHW increased to a maximum of 9 at 13.2% before diminishing, indicating the maximum... 

Since MEs have become commercially valuable for tertiary oil recovery, in the food and pharmaceutical industry, their characterization has become a pertinent feature of many publications dealing with this type of colloidal systems [4,7,38]. Knowing the microstructure of an ME is of great importance as the phase behavior will influence the ability to solubilize compounds and can determine drug release [39] or influence the manufacture of polymeric nanoparticles from these systems [40]. 

In designing cellular tissue, the diffusion rate of the solubilized compound is important in order to determine the rate of release of drugs or transport of nutrients and metabolites. The diffusion of nutrients, metabolites and other solubilized compounds depends on many factors, including the morphology of the network, the chemical composition of the hydrogel, the water content, the concentration of solubiUzed compounds and the level of the material swelling [7]. 

Thus far only processes involving motion of the surfactant as a whole have been mentioned. Other processes may occur in micellar solutions internal motion of the surfactant alkyl chains within the micelles exchange of cormterions between free and micelle-bound states and fast changes of micelle shape, among others. Also in the case of solubilized systems, i.e., micellar solutions that have solubilized compounds that are sparingly soluble in water, the solubilizate may exchange between micelles and the intermicellar solution. The dynamics of the exchange of counterions and of solubilizates are reviewed later. The dynamics of internal motions of the surfactant alkyl chains are not dealt with in this chapter, but some information and references can be found in Chapter 5, Section V. Some information on the fluctuations of micelle shapes can be found in Chapter 1, Section III.B. 

Solubilized systems refer to surfactant solutions in which the micelles have solubilized compounds (solubilizates) that are generally poorly soluble in water. Most studies address the rate constants for the exchange of the solubilizate. A few studies examine the effect of solubilizate other than cosrufac-tants on the surfactant exchange and micelle forma-tion/breakdown. 

As stated, typical dry cleaning detergents contain surfactants, solvents, cosolvents, organotropic (dissolving) and hydrotropic (solubilizing) compounds, water, and salts. 

The capacity of solubilizing compounds in the droplets of a nano-emulsion gives the possibility of developing applications, implying the transport of these compounds through a continuous phase in which they are insoluble. Pharmaceutical and cosmetic applications for which nonpolar compounds are solubilized in oil droplets dispersed in aqueous media would be typical, and other possible applications in food or agrochemical fields have also been described [1,2],... 

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